Preclinical Bioassay of a Polypropylene Mesh for Hernia Repair Pretreated with Antibacterial Solutions of Chlorhexidine and Allicin: An In Vivo Study

Introduction

Prosthetic mesh infection constitutes one of the major complications following hernia repair. Antimicrobial, non-antibiotic biomaterials have the potential to reduce bacterial adhesion to the mesh surface and adjacent tissues while avoiding the development of novel antibiotic resistance. This study assesses the efficacy of presoaking reticular polypropylene meshes in chlorhexidine or a chlorhexidine and allicin combination (a natural antibacterial agent) for preventing bacterial infection in a short-time hernia-repair rabbit model.

Methods

Partial hernia defects (5 x 2 cm) were created on the lateral right side of the abdominal wall of New Zealand White rabbits (n = 21). The defects were inoculated with 0.5 mL of a 10⁶ CFU/mL Staphylococcus aureus ATCC25923 strain and repaired with a DualMesh Plus antimicrobial mesh or a Surgipro mesh presoaked in either chlorhexidine (0.05%) or allicin-chlorhexidine (900 μg/mL-0.05%). Fourteen days post-implant, mesh contraction was measured and tissue specimens were harvested to evaluate bacterial adhesion to the implant surface (via sonication, S. aureus immunolabeling), host-tissue incorporation (via staining, scanning electron microscopy) and macrophage response (via RAM-11 immunolabeling).

Results

The polypropylene mesh showed improved tissue integration relative to the DualMesh Plus. Both the DualMesh Plus and the chlorhexidine-soaked polypropylene meshes exhibited high bacterial clearance, with the latter material showing lower bacterial yields. The implants from the allicin-chlorhexidine group displayed a neoformed tissue containing differently sized abscesses and living bacteria, as well as a diminished macrophage response. The allicin-chlorhexidine coated implants exhibited the highest contraction.

Conclusions

The presoaking of reticular polypropylene materials with a low concentration of chlorhexidine provides the mesh with antibacterial activity without disrupting tissue integration. Due to the similarities found with the antimicrobial DualMesh Plus material, the chlorhexidine concentration tested could be utilized as a prophylactic treatment to resist infection by prosthetic mesh during hernia repair.     

Lavage with Allicin in Combination with Vancomycin Inhibits Biofilm Formation by Staphylococcus epidermidis in a Rabbit Model of Prosthetic Joint Infection

Background and Aim

The present anti-infection strategy for prosthetic joint infections (PJI) includes the use of antibiotics and surgical treatments, but the bacterial eradication rates are still low. One of the major challenges is the formation of biofilm causing poor bacterial eradication. Recently it has been reported that allicin (diallyl thiosulphinate), an antibacterial principle of garlic, can inhibit bacteria adherence and prevent biofilm formation in vitro. However, whether allicin could inhibit biofilm formation in vivo is unknown. The aim of this study was to investigate the effects of allicin on biofilm formation, and whether allicin could potentiate the bactericidal effect of vancomycin in a rabbit PJI model.

Methods

A sterile stainless-steel screw with a sterile ultra-high molecular weight polyethylene washer was inserted into the lateral femoral condyle of the right hind knee joint of rabbit, and 1 mL inoculum containing 10⁴ colony-forming units of Staphylococcus epidermidis was inoculated into the knee joint (n = 32). Fourteen days later, rabbits randomly received one of the following 4 treatments using continuous lavages: normal saline, vancomycin (20 mcg/mL), allicin (4 mg/L), or allicin (4 mg/L) plus vancomycin (20 mcg/mL). Three days later, the washer surface biofilm formation was examined by scanning electron microscopy (SEM). The bacterial counts within the biofilm of implanted screws were determined by bacterial culture.

Results

The lowest number of viable bacterial counts of Staphylococcus epidermidis recovered from the biofilm was in the rabbits treated with allicin plus vancomycin (P<0.01 vs. all other groups). The biofilm formation was significantly reduced or undetectable by SEM in rabbits receiving allicin or allicin plus vancomycin.

Conclusion

Intra-articular allicincan inhibit biofilm formation and enhance the bactericidal effect of vancomycin on implant surface in vivo. Allicin in combination with vancomycin may be a useful anti-infection strategy for the treatment of PJI.     

Cost-Effectiveness Analysis of a Transparent Antimicrobial Dressing for Managing Central Venous and Arterial Catheters in Intensive Care Units

Objective

To model the cost-effectiveness impact of routine use of an antimicrobial chlorhexidine gluconate-containing securement dressing compared to non-antimicrobial transparent dressings for the protection of central vascular lines in intensive care unit patients.

Design

This study uses a novel health economic model to estimate the cost-effectiveness of using the chlorhexidine gluconate dressing versus transparent dressings in a French intensive care unit scenario. The 30-day time non-homogeneous markovian model comprises eight health states. The probabilities of events derive from a multicentre (12 French intensive care units) randomized controlled trial. 1,000 Monte Carlo simulations of 1,000 patients per dressing strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The outcome is the number of catheter-related bloodstream infections avoided. Costs of intensive care unit stay are based on a recent French multicentre study and the cost-effectiveness criterion is the cost per catheter-related bloodstream infections avoided. The incremental net monetary benefit per patient is also estimated.

Patients

1000 patients per group simulated based on the source randomized controlled trial involving 1,879 adults expected to require intravascular catheterization for 48 hours.

Intervention

Chlorhexidine Gluconate-containing securement dressing compared to non-antimicrobial transparent dressings.

Results

The chlorhexidine gluconate dressing prevents 11.8 infections /1,000 patients (95% confidence interval: [3.85; 19.64]) with a number needed to treat of 85 patients. The mean cost difference per patient of €141 is not statistically significant (95% confidence interval: [€-975; €1,258]). The incremental cost-effectiveness ratio is of €12,046 per catheter-related bloodstream infection prevented, and the incremental net monetary benefit per patient is of €344.88.

Conclusions

According to the base case scenario, the chlorhexidine gluconate dressing is more cost-effective than the reference dressing.

Trial Registration

This model is based on the data from the RCT registered with www.clinicaltrials.gov (NCT01189682).     

Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis

Background

Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2–17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model.

Methodology

Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7–12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits.

Results

On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops.

Conclusions

Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.     

Antimicrobial Activity of a Novel Vascular Access Film Dressing Containing Chlorhexidine Gluconate

Background

Covering insertion sites with chlorhexidine impregnated dressings has been proven to be clinically effective in reducing catheter related blood stream infections (CR-BSI). Two chlorhexidine gluconate (CHG)-impregnated dressings are commercially available, a polyurethane foam disk and a film dressing containing a chlorhexidine gluconate-impregnated gel pad. While both have demonstrated efficacy in clinical settings, the major drawback of high cost and impaired IV insertion site visibility limits their usage. A new, simple film dressing containing CHG within its adhesive layer is now available. The objective of this study was to test the in vitro antimicrobial efficacy of the new dressing in comparison to the CHG-impregnated gel dressing.

Methods

Quantitative aliquots of suspensions (concentration of 1.0x10⁶ to 5.0x10⁶ cfu/sample) of clinically relevant challenge organisms (Staphylococcus species, gram-negative bacilli, Candida albicans) were incubated in contact with the new CHG-containing film dressing, a placebo version of the same (negative control) and the commercially available CHG-impregnated gel dressing (positive control). Serial dilutions of the surviving organisms were quantified using the pour plate after 1, 3, 5, and 7 days of incubation in order to calculate an antimicrobial log₁₀ reduction for each organism/dressing combination at each point in time.

Results

The new CHG-containing film dressing delivered greater than 5.0 log₁₀ reduction throughout the 7 days on all aerobic gram-negative bacilli and Staphylococcus species tested. As of day 1 the CHG-containing film dressing provided greater than 5.0 log₁₀ reduction on Candida albicans. There were no statistically significant differences in the log₁₀ reduction between the two dressings tested.

Conclusion

The new CHG-containing film dressing was found to be as effective as the chlorhexidine gluconate-impregnated gel dressing on clinically relevant microbes.     

Assessments of Thioridazine as a Helper Compound to Dicloxacillin against Methicillin-Resistant Staphylococcus aureus: In Vivo Trials in a Mouse Peritonitis Model

Introduction

The rise in antimicrobial resistance is a major global concern and requires new treatment strategies. The use of helper compounds, such as thioridazine (TDZ), an antipsychotic drug, in combination with traditional antibiotics must be investigated.

Objectives

The aim of this study was to investigate the efficacy of TDZ as a helper compound for dicloxacillin (DCX) against methicillin-resistant Staphylococcus aureus (MRSA) in vivo, and compare the combination treatment of DCX+TDZ with vancomycin (VAN).

Methods

Mice were inoculated with an intraperitoneal (IP) injection of MRSA (10⁸ CFU) and treated in a 12-hour cycle for 48 hours. By termination, bacterial quantities in a peritoneal flush, spleen and kidneys were obtained. In the main trial the drugs were administered subcutaneously in five treatment groups: 1) DCX, 2) TDZ, 3) DCX+TDZ, 4) VAN, 5) SALINE. Additional smaller studies with IP administration and higher subcutaneous dosages (×1.5 and ×4) of the drugs were subsequently performed.

Results

In the main trial no significant differences were found between DCX+TDZ and DCX or TDZ alone (p≥0.121–0.999). VAN performed significantly better than DCX+TDZ on all bacteriological endpoints (p<0.001). Higher subcutaneous dosages of DCX and TDZ improved the antibacterial efficacy, but the combination treatment was still not significantly better than monotherapy. IP drug administration of DCX+TDZ revealed a significantly better antibacterial effect than DCX or TDZ alone (p<0.001) but not significantly different from VAN (p>0.999).

Conclusion

In conclusion, TDZ did not prove to be a viable helper compound for dicloxacillin against MRSA in subcutaneous systemic treatment. However, IP-administration of DCX+TDZ, directly at the infection site resulted in a synergetic effect, with efficacy comparable to that of VAN.     

Intraocular Pressure Changes during Accommodation in Progressing Myopes,Stable Myopes and Emmetropes

Purpose

To investigate the changes of intraocular pressure (IOP) induced by 3-diopter (3 D) accommodation in progressing myopes, stable myopes and emmetropes.

Design

Cross-sectional study.

Participants

318 subjects including 270 myopes and 48 emmetropes.

Methods

195 progressing myopes, 75 stable myopes and 48 emmetropes participated in this study. All subjects had their IOP measured using iCare rebound tonometer while accommodative stimuli of 0 D and 3 D were presented.

Main Outcome Measures

IOP values without accommodation and with 3 D accommodation were measured in all subjects. Baseline IOPs and IOP changes were compared within and between groups.

Results

There was no significant difference in IOPs between progressing myopes, stable myopes and emmetropes when no accommodation was induced (17.47±3.46, 16.62±2.98 and 16.80±3.62 respectively, p>0.05). IOP experienced an insignificantly slight decrease after 3 D accommodation in three groups (mean change -0.19±2.16, -0.03±1.68 and -0.39±2.65 respectively, p>0.05). Subgroup analysis showed in progressing myopic group, IOP of children (<18 years old) declined with accommodation while IOP of adults (≥18 years) increased, and the difference was statistically significant (p = 0.008). However, after excluding the age factor, accommodation induced IOP changes of high progressing myopes (≤-6 D), low, moderate and non-myopes (>-6 D) was not significantly different after Bonferroni correction (p = 0.838).

Conclusions

Although no difference was detected between the baseline IOPs and accommodation induced IOP changes in progressing myopes, stable myopes and emmetropes, this study found accommodation could cause transient IOP elevation in adult progressing myopes.     

Effect of Antibiotics on Gut Microbiota,Gut Hormones and Glucose Metabolism

Objective

The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans.

Methods

Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition.

Results

Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release.

Conclusion

As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males.

Trial Registration

clinicaltrials.gov NCT01633762     

Cost-Effectiveness of Financial Incentives to Promote Adherence to Depot Antipsychotic Medication: Economic Evaluation of a Cluster-Randomised Controlled Trial

Background

Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined.

Methods

Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period).

Findings

Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving ''good'' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5% at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence.

Interpretation

Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention.

Trial Registration

ISRCTN.com 77769281     

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.     

A Biofilm Pocket Model to Evaluate Different Non-Surgical Periodontal Treatment Modalities in Terms of Biofilm Removal and Reformation,Surface Alterations and Attachment of Periodontal Ligament Fibroblasts

Background and Aim

There is a lack of suitable in vitro models to evaluate various treatment modalities intending to remove subgingival bacterial biofilm. Consequently, the aims of this in vitro-study were: a) to establish a pocket model enabling mechanical removal of biofilm and b) to evaluate repeated non-surgical periodontal treatment with respect to biofilm removal and reformation, surface alterations, tooth hard-substance-loss, and attachment of periodontal ligament (PDL) fibroblasts.

Material and Methods

Standardized human dentin specimens were colonized by multi-species biofilms for 3.5 days and subsequently placed into artificially created pockets. Non-surgical periodontal treatment was performed as follows: a) hand-instrumentation with curettes (CUR), b) ultrasonication (US), c) subgingival air-polishing using erythritol (EAP) and d) subgingival air-polishing using erythritol combined with chlorhexidine digluconate (EAP-CHX). The reduction and recolonization of bacterial counts, surface roughness (Ra and Rz), the caused tooth substance-loss (thickness) as well as the attachment of PDL fibroblasts were evaluated and statistically analyzed by means of ANOVA with Post-Hoc LSD.

Results

After 5 treatments, bacterial reduction in biofilms was highest when applying EAP-CHX (4 log10). The lowest reduction was found after CUR (2 log10). Additionally, substance-loss was the highest when using CUR (128±40 µm) in comparison with US (14±12 µm), EAP (6±7 µm) and EAP-CHX (11±10) µm). Surface was roughened when using CUR and US. Surfaces exposed to US and to EAP attracted the highest numbers of PDL fibroblasts.

Conclusion

The established biofilm model simulating a periodontal pocket combined with interchangeable placements of test specimens with multi-species biofilms enables the evaluation of different non-surgical treatment modalities on biofilm removal and surface alterations. Compared to hand instrumentation the application of ultrasonication and of air-polishing with erythritol prevents from substance-loss and results in a smooth surface with nearly no residual biofilm that promotes the reattachment of PDL fibroblasts.     

Thyroid Hormone Activates Brown Adipose Tissue and Increases Non-Shivering Thermogenesis - A Cohort Study in a Group of Thyroid Carcinoma Patients

Background/Objectives

Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity.

Subjects/Methods

This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used.

Results

Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUV^Mean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039).

Conclusions

Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02499471","term_id":"NCT02499471"}}NCT02499471     

Developing Repair Materials for Stress Urinary Incontinence to Withstand Dynamic Distension

Background

Polypropylene mesh used as a mid-urethral sling is associated with severe clinical complications in a significant minority of patients. Current in vitro mechanical testing shows that polypropylene responds inadequately to mechanical distension and is also poor at supporting cell proliferation.

Aims and Objectives

Our objective therefore is to produce materials with more appropriate mechanical properties for use as a sling material but which can also support cell integration.

Methods

Scaffolds of two polyurethanes (PU), poly-L-lactic acid (PLA) and co-polymers of the two were produced by electrospinning. Mechanical properties of materials were assessed and compared to polypropylene. The interaction of adipose derived stem cells (ADSC) with the scaffolds was also assessed. Uniaxial tensiometry of scaffolds was performed before and after seven days of cyclical distension. Cell penetration (using DAPI and a fluorescent red cell tracker dye), viability (AlamarBlue assay) and total collagen production (Sirius red assay) were measured for ADSC cultured on scaffolds.

Results

Polypropylene was stronger than polyurethanes and PLA. However, polypropylene mesh deformed plastically after 7 days of sustained cyclical distention, while polyurethanes maintained their elasticity. Scaffolds of PU containing PLA were weaker and stiffer than PU or polypropylene but were significantly better than PU scaffolds alone at supporting ADSC.

Conclusions

Therefore, prolonged mechanical distension in vitro causes polypropylene to fail. Materials with more appropriate mechanical properties for use as sling materials can be produced using PU. Combining PLA with PU greatly improves interaction of cells with this material.     

Diffusion Tensor Magnetic Resonance Imaging of Trigeminal Nerves in Relapsing Herpetic Keratouveitis

Background

Corneal hypoesthesia is the landmark of HSV and VZV keratitis and can lead to neurotrophic keratitis. Diffusion tensor imaging (DTI) is a new magnetic resonance imaging (MRI) derived technique, which offers possibilities to study axonal architecture. We aimed at assessing the potential impact of recurrent HSV or VZV-related keratitis on the axonal architecture of trigeminal nerves using DTI.

Design

Prospective non-interventional study.

Participants

Twelve patients and 24 controls.

Methods

DTI using MRI of the trigeminal fibers and corneal esthesiometry using the Cochet-Bonnet esthesiometer were acquired for patients affected by unilateral and recurrent HSV or VZV-related keratitis (3 months after the last corneal inflammatory event), and control subjects with no history of ocular or neuronal disease affecting the trigeminal pathways.

Main Outcome Measures

Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared between the 2 eyes of both patients and controls, and correlated with corneal esthesiometry.

Results

FA was lower in the trigeminal fibers ipsilateral to the affected eye compared to the non-affected side (0.39±0.02 versus 0.46±0.04, P=0.03). This difference was more important than the intra-individual variability observed in controls. Concomitantly, the asymmetry in ADC results was significantly correlated with the loss of corneal sensitivity in the affected eye.

Conclusions

Corneal hypoesthesia related to HSV and VZV keratitis is associated with persistent modifications in the architecture and functionality of the trigeminal fibers. These results add further explanation to the pathogenesis of HSV and VZV-induced neurotrophic keratitis, which may occur despite an apparent quiescence of the disease.     

Induced Sporicidal Activity of Chlorhexidine against Clostridium difficile Spores under Altered Physical and Chemical Conditions

Background

Chlorhexidine is a broad-spectrum antimicrobial commonly used to disinfect the skin of patients to reduce the risk of healthcare-associated infections. Because chlorhexidine is not sporicidal, it is not anticipated that it would have an impact on skin contamination with Clostridium difficile, the most important cause of healthcare-associated diarrhea. However, although chlorhexidine is not sporicidal as it is used in healthcare settings, it has been reported to kill spores of Bacillus species under altered physical and chemical conditions that disrupt the spore’s protective barriers (e.g., heat, ultrasonication, alcohol, or elevated pH). Here, we tested the hypothesis that similarly altered physical and chemical conditions result in enhanced sporicidal activity of chlorhexidine against C. difficile spores.

Principal Findings

C. difficile spores became susceptible to heat killing at 80°C within 15 minutes in the presence of chlorhexidine, as opposed to spores suspended in water which remained viable. The extent to which the spores were reduced was directly proportional to the concentration of chlorhexidine in solution, with no viable spores recovered after 15 minutes of incubation in 0.04%–0.0004% w/v chlorhexidine solutions at 80°C. Reduction of spores exposed to 4% w/v chlorhexidine solutions at moderate temperatures (37°C and 55°C) was enhanced by the presence of 70% ethanol. However, complete elimination of spores was not achieved until 3 hours of incubation at 55°C. Elevating the pH to ≥9.5 significantly enhanced the killing of spores in either aqueous or alcoholic chlorhexidine solutions.

Conclusions

Physical and chemical conditions that alter the protective barriers of C. difficile spores convey sporicidal activity to chlorhexidine. Further studies are necessary to identify additional agents that may allow chlorhexidine to reach its target within the spore.     

No Outbreak of Vancomycin and Linezolid Resistance in Staphylococcal Pneumonia over a 10-Year Period

Background

Staphylococci can cause wound infections and community- and nosocomial-acquired pneumonia, among a range of illnesses. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) have been rapidly increasing as a cause of infections worldwide in recent decades. Numerous reports indicate that S. aureus and MRSA are becoming resistant to many antibiotics, which makes them very dangerous. Therefore, this study retrospectively investigated the resistance to antimicrobial agents in all hospitalized patients suffering from community- or nosocomial-acquired pneumonia due to S. aureus and MRSA.

Methods

Information from the study groups suffering from either community- or nosocomial-acquired pneumonia caused by S. aureus or MRSA was gathered by searching records from 2004 to 2014 at the HELIOS Clinic Wuppertal, Witten/Herdecke University, Germany. The findings of antibiotic resistance were analyzed after the evaluation of susceptibility testing for S. aureus and MRSA.

Results

Total of 147 patients (63.9%, 95% CI 57.5%–69.8%), mean age 67.9 ± 18.5 years, with pneumonia triggered by S. aureus, and 83 patients (36.1%, 95% CI 30.2%–42.5%), mean age 72.3 ± 13.8 years, with pneumonia due to MRSA. S. aureus and MRSA developed no resistance to vancomycin (P = 0.019 vs. < 0.0001, respectively) or linezolid (P = 0.342 vs. < 0.0001, respectively). MRSA (95.3%) and S. aureus (56.3%) showed a high resistance to penicillin. MRSA (87.7%) was also found to have a high antibiotic resistance against ß-lactam antibiotics, compared to S. aureus (9.6%). Furthermore, MRSA compared to S. aureus, respectively, had increased antibiotic resistance to ciprofloxacin (90.1% vs. 17.0%), cefazolin (89.7% vs. 10.2%), cefuroxime (89.0% vs. 9.1%), levofloxacin (88.2% vs. 18.4%), clindamycin (78.0% vs. 14.7%), and erythromycin (76.5% vs. 20.8%).

Conclusion

No development of resistance was found to vancomycin and linezolid in patients with pneumonia caused by S. aureus and MRSA.     

Retropupillary Fixation of Iris-Claw Intraocular Lens for Aphakic Eyes in Children

Purpose

To report outcome, complications and safety of retropupillary fixated iris-claw intraocular lenses in a pediatric population.

Design

Retrospective study.

Patients and Methods

Ten consecutive pediatric patients (15 eyes) underwent placement of retropupillary fixated iris-claw intraocular lenses between October 2007 and July 2013 at the Department of Ophthalmology, Medical University Graz and General Hospital Klagenfurt, Austria. Postoperative visual acuity and complications were analyzed.

Results

Median final best-corrected visual acuity improved by 0.12 logMAR from preoperative baseline. Mean postoperative spherical equivalent was -0.05 ± 1.76 D. No serious complications were observed intra- or postoperatively during the entire follow-up period of up to 40 months. One patient experienced a haptic disenclavation with IOL subluxation immediately after a car accident.

Conclusion

Our study demonstrates that iris-claw intraocular lens implantation behind the iris is safe in children with lack of capsular support and yields excellent visual outcome with low complication rate.