Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.

Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Locally delivered adjuvant biofilm-penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection.

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.

Metronidazole-induced encephalopathy caused by hyperbaric oxygen therapy in a patient with mandibular osteomyelitis.

Metronidazole (MNZ) is prescribed for the treatment of infection caused by anaerobic bacteria and protozoa. Metronidazole-induced encephalopathy (MIE) has been known to be a side-effect, although its onset ratio is unclear. However, to the best of our knowledge, MIE associated with hyperbaric oxygen therapy (HBO) has not been previously reported. Here, we present the case of a 68-year-old man with mandibular osteomyelitis who received metronidazole for 49 days and received five times HBO therapy. He visited our hospital for evaluation and treatment of peripheral neuropathy, speech disturbance, nausea, and disturbance of gait after 47 days of initiating metronidazole treatment. Brain magnetic resonance imaging revealed hyperintense lesions in the cerebellar dentate nuclei, which was consistent with MIE. The patient's ataxic symptoms improved in 15 days after the discontinuation of MNZ. This is the first report demonstrating case of MIE could be related with HBO, as far as we had searched.

The Pros and Cons of Cystic Fibrosis (CF) Patient Use of Herbal Supplements Containing Pulmonaria officinalis L. Extract: the Evidence from an In Vitro Study on Staphylococcus aureus CF Clinical Isolates.

The justification for the use of herbal supplements with Pulmonaria officinalis L. extract (POE) in the case of staphylococcal lung colonization/infections characteristic for cystic fibrosis (CF), was examined in vitro. The impact of POE phenolic-rich fraction on the virulence attributes of CF-associated Staphylococcus aureus (S. aureus) clinical strains has been assessed, including pathogen adhesion, biofilm formation on native and protein-conditioned surfaces (mucin, elastin), mature biofilm eradication, staphylococcal protein A expression, α-toxin release, and S. a. adhesion to A549 cells. Cytotoxicity of the extract to lung epithelial cells was also investigated. It was found that POE has bacteriostatic effects at MIC 1⁻2 mg/mL, recognized as of limited efficacy, but at MIC/subMICs it targeted virulence not viability. It usually decreased S. aureus adhesion and less frequently inhibited biofilm formation on native and protein-conditioned surfaces. Observed effect seems to be related to significant reduction by POE of sortase A activity. However, in some cases POE favored the creation of biofilm by staphylococci and S. aureus adhesion to the lung epithelium was not limited. On the other side POE caused significant decrease of S. a. α-toxin synthesis and slightly weakened the expression of SpA. When used at supraMICs POE eradicated mature biofilm, but in some cases with unsatisfying outcomes. Promisingly, POE has been recognized as a safe product, with no cytotoxicity up to 4 mg/mL. These results reflect the positive, negative or neutral anti-staphylococcal properties of POE. It seems that POE may be beneficial as a prophylactic, but not as a therapeutic or supportive agent in the area of CF-integrative medicine. However, introduction the official recommendations needs further in vivo studies.

Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. / Insulina tópica en queratopatía neurotrófica tras resección de neurinoma del acústico.

CASE REPORT: A patient with a history of surgical resection of an acoustic neuroma presented with involvement of both the left facial nerve and the left trigeminal nerve. She initially consulted for exposure keratitis, but two weeks later presented with an infectious keratitis. After taking the corneal sample, she presented with persistent epithelial defect, which did not respond to medical management. Topical insulin was indicated, and a decrease in the area of the lesion was seen in the following 5 days. A therapeutic contact lens was also placed at that time and finally, two weeks after the initiation of insulin, the epithelial defect completely closed. DISCUSSION: This was a complex case due to the confluence of facial paralysis, neurotrophic keratitis, and infectious keratitis, which finally had a successful outcome. Topical insulin can be an effective adjuvant therapy in cases of neurotrophic ulcers that do not respond to standard therapy.

Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint Infection.

BACKGROUND: Despite recent advances, infection remains the most common etiology of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D) deficiency correlates with the frequency of periprosthetic joint infection (PJI). We endeavored to examine whether 25D3 deficiency leads to increased bacterial burden in vivo in an established mouse model of PJI and, if so, whether this effect can be reversed by preoperative 25D3 supplementation. METHODS: Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n = 20) were "rescued" with 1 intraperitoneal dose of 25D3 at 3 days before surgery. A stainless steel implant was inserted into the knee joint and the joint space was inoculated with bioluminescent Staphylococcus aureus (1 × 10 colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D3 levels 3 days before surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21, and CFUs were quantified after culture. Myeloperoxidase (MPO) and ß-N-acetylglucosaminidase (NAG) were assayed to look at neutrophil infiltration and activated tissue macrophage recruitment, respectively. RESULTS: Serum values confirmed 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D3-deficient group. CFU counts from the joint tissue and implant were also significantly greater in this group (p < 0.05). Rescue treatment significantly decreased bacterial burden and neutrophil infiltration (p < 0.05). Compared with the 25D3-sufficient and 25D3-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient group. CONCLUSIONS: This study demonstrated in vivo in a mouse model of PJI that (1) 25D3 deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D3. CLINICAL RELEVANCE: Considering that >65% of patients undergoing arthroplasty have insufficient or low levels of total 25D and that 25D levels can be replenished with ease using a U.S. Food and Drug Administration (FDA)-approved, oral 25D3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.

Intracavitary and Systemic Daptomycin for Successful Treatment of a Postpneumonectomy Intrathoracic Infection.

Treatment of an infected postpneumonectomy cavity is very difficult. We present a patient with an infection of a postpneumonectomy cavity by Staphylococcus epidermidis treated with local daptomycin for different dwell times, maintaining high antibiotic levels above the MIC. Clinical and microbiological cure were achieved successfully.

Antibiotic susceptibility profiles of ocular and nasal flora in patients undergoing cataract surgery in Taiwan: an observational and cross-sectional study.

OBJECTIVE: To investigate the conjunctival and nasal flora and the antibiotic susceptibility profiles of isolates from patients undergoing cataract surgery. DESIGN: Observational and cross-sectional study. SETTING: A single-centre study in Taiwan. PARTICIPANTS: 128 consecutive patients precataract surgery. PRIMARY AND SECONDARY OUTCOME MEASURES METHODS: Conjunctival and nasal cultures were prospectively obtained from 128 patients on the day of cataract surgery before instillation of ophthalmic solutions in our hospital. Isolates and antibiotic susceptibility profiles were identified through standard microbiological techniques. Participants were asked to complete a questionnaire on healthcare-associated factors. RESULTS: The positive culture rate from conjunctiva was 26.6%, yielding 84 isolates. Coagulase-negative Staphylococci were the most commonly isolated organisms (45.2%), and 35% of staphylococcal isolates were methicillin-resistant. Among staphylococcal isolates, all were susceptible to vancomycin, and 75%-82.5% were susceptible to fluoroquinolones. Methicillin-resistant isolates were significantly less susceptible than their methicillin-sensitive counterparts to tobramycin, the most commonly used prophylactic antibiotic in our hospital (28.6% vs 69.2%; p=0.005). The positive culture rate from nares for Staphylococcus aureus was 21.9%, and six isolates were methicillin-resistant. No subjects had S. aureus colonisation on conjunctiva and nares simultaneously. There were no associated risk factors for colonisation of methicillin-resistant Staphylococci. CONCLUSION: The most common conjunctival bacterial isolate of patients undergoing cataract surgery was coagulase-negative Staphylococci in Taiwan. Because of predominant antibiotic preferences and selective antibiotic pressures, Staphylococci were more susceptible to fluoroquinolones but less to tobramycin than in other reports. Additionally, methicillin-resistant Staphylococci exhibited co-resistance to tobramycin but not to fluoroquinolones.

Postoperative infectious complications in patients undergoing holmium laser enucleation of the prostate: Risk factors and microbiological analysis.

OBJECTIVES: To examine the incidence of postoperative bacteriuria and febrile complications, and to investigate bacterial strains in the urine of patients undergoing holmium laser enucleation of the prostate. METHODS: We retrospectively analyzed 190 evaluable patients treated with holmium laser enucleation of the prostate at the Gifu University Hospital, Gifu, Japan, between September 2005 and May 2014. All patients presented with lower urinary tract symptoms as a result of benign prostatic hyperplasia. We also evaluated the causative bacteria and compared the findings with the results of preoperative urine cultures. We analyzed the relationship between the emergence of postoperative febrile complications, antibiotic prophylaxis, patient background and surgical procedure. RESULTS: The frequency of bacterial isolation in preoperative and postoperative urine cultures was 41% and 23%, respectively. Preoperatively, Enterococcus faecalis was the most frequently cultured bacteria, second was methicillin-resistant Staphylococcus epidermidis, and third was Escherichia coli. Postoperatively, Enterococcus faecalis was still the most frequently cultured bacteria, whereas the second was Escherichia coli. Risk factors for postoperative bacteriuria were evaluated. Multivariate analysis showed that the rate of postoperative bacteriuria in patients who had taken dutasteride preoperatively was significantly lower than that in the other patients. Risk factors for febrile complications could not be identified. CONCLUSIONS: The use of perioperative prophylactic antibacterial agents for holmium laser enucleation of the prostate keeps the rate of postoperative infectious complications low. Dutasteride treatment administered before surgery might reduce the risk of postoperative bacteriuria.

Atlanto-axial infection after acupuncture.

A 67-year-old man presented with neck cellulitis following acupuncture for cervical spondylosis. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus Increased neck pain and bacteraemia prompted MRI, which showed atlanto-axial septic arthritis without signs of infection of the tissues between the superficial cellulitic area and the atlanto-axial joint, thus making direct extension of infection unlikely. It is more likely that haematogenous spread of infection resulted in seeding in the atlanto-axial joint, with the proximity of the arthritis and acupuncture site being coincidental. Acupuncture is a treatment option for some indolent pain conditions. As such, acupuncture services are likely to be more frequently utilised. A history of acupuncture is rarely requested by the admitting doctor and seldom offered voluntarily by the patient, especially where the site of infection due to haematogenous spread is distant from the needling location. Awareness of infectious complications following acupuncture can reduce morbidity through early intervention.

Cervical spinal epidural abscess following acupuncture and wet-cupping therapy: A case report.

OBJECTIVE: Report of an uncommon complication of acupuncture and wet cupping. METHODS: A 54-year-old man presented with neck pain and fever. Magnetic resonance imaging of the cervical spine revealed an epidural abscess at C4 to T2. RESULTS: The symptoms related to epidural abscess resolved partially after treatment with antibiotics. CONCLUSION: Acupuncture and wet-cupping therapy should be taken into consideration as a cause of spinal epidural abscesses in patients who present with neck pain and fever. Furthermore, acupuncture and wet-cupping practitioners should pay attention to hygienic measures.

Atlanto-axial infection after acupuncture.

A 67-year-old man presented with neck cellulitis following acupuncture for cervical spondylosis. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus. Increased neck pain and bacteraemia prompted MRI, which showed atlanto-axial septic arthritis without signs of infection of the tissues between the superficial cellulitic area and the atlanto-axial joint, thus making direct extension of infection unlikely. It is more likely that haematogenous spread of infection resulted in seeding in the atlanto-axial joint, with the proximity of the arthritis and acupuncture site being coincidental. Acupuncture is a treatment option for some indolent pain conditions. As such, acupuncture services are likely to be more frequently utilised. A history of acupuncture is rarely requested by the admitting doctor and seldom offered voluntarily by the patient, especially where the site of infection due to haematogenous spread is distant from the needling location. Awareness of infectious complications following acupuncture can reduce morbidity through early intervention.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. METHODS: A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. RESULTS: Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). CONCLUSIONS: Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality.

Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the treatment of postoperative endophthalmitis.

PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for postoperative endophthalmitis. METHODS: First, an experimental laboratory model using Staphylococcus aureus was used to evaluate the bactericidal effect of PI-BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted, followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of 0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using 0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye at the beginning but not at completion of surgery. In all four eyes, endophthalmitis was resolved with no adverse events. Ocular toxicity was not observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when used as irrigation solution in vitrectomy. In 4 cases of postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative antibiotics resolved endophthalmitis.

Nasal carriage of mecA-positive methicillin-resistant Staphylococcus aureus in pigs exhibits dose-response to zinc supplementation.

Zinc (Zn) is often supplemented at elevated concentrations in swine diets, particularly in piglets, to prevent enteric infections and promote growth. Previous studies from Denmark have suggested a genetic linkage and a phenotypic association between Zn resistance, encoded by czrC, and methicillin-resistance conferred by mecA in Staphylococcus aureus. Such an association has not been reported in the U.S. swine population. We conducted an analysis of the effects of Zn, supplemented as zinc oxide (ZnO), on the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in nursery (n=40) and finisher pigs (n=40) enrolled in a nutritional study. Nasal swabs, collected from nursery and finisher pigs, were inoculated onto MRSA CHROMagar and presumptive MRSA colonies were tested for the presence of mecA and czrC genes by polymerase chain reaction. Zinc susceptibility was determined by the agar dilution method. The prevalence of mecA-positive MRSA was 10% (4/40) and 20% (8/40) among nursery and finisher pigs, respectively. Of the 12 mecA-positive S. aureus isolates, 7 had the czrC gene (58.3%) compared to none among the 68 mecA-negative isolates. The presence of both mecA (p=0.002) and czrC (p=0.006) genes were positively associated with higher levels of Zn supplementation. The median minimum inhibitory concentrations of Zn for czrC-positive and czrC-negative isolates were 12 and 2 mM, respectively (p<0.0001). The link between czrC and mecA genes suggests the importance of elevated Zn supplementation in the co-selection and propagation of methicillin resistance among S. aureus in pigs.