Impact of pH modification of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus).

BACKGROUND: Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation. RESULTS: Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug's bioavailability. The MIC90 of the most hazardous bacteria isolated from equines' eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239-342 min) and aqueous humor (238-330 min) with the modified tobramycin solution. CONCLUSIONS: Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys' ophthalmic infections at a pH of 8.26, isotonic with the donkeys' tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.

The application of topical antibiotics for the prevention of infections in primary joint arthroplasty. An umbrella review of systematic reviews and meta-analysis.

This umbrella review aim to explore the effect of topical antibiotics in infection prevention after primary joint arthroplasty, and provide a specific theoretical basis for clinical treatment. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, EMBASE, Medline, and the Cochrane Library on infection prevention by topical antibiotics from inception to 10 April 2023. The two researchers individually and strictly screened the literature according to the inclusion and exclusion criteria, performed the literature quality evaluation and data extraction, and used Stata 17 for data analysis. This study included six studies with one systematic review and five meta-analyses. The pooled analysis showed that topical antibiotic administration effectively reduced the incidence of overall infection and periprosthetic joint infection. However, it does not reduce the risk of superficial infection. Besides, the topic of antibiotics significantly increases the incidence of other sterile complications of the incision. According to the current evidence, topical application of antibiotics can reduce the incidence of overall infection and periprosthetic joint infection after primary joint arthroplasty. Although it increases the incidence of complications such as delayed healing of incisions, the pros and cons should be weighed in clinical decision making. However, they should not be discarded due to side effects.

Incidence of infection in carpal tunnel surgery with and without the use of local antibiotics.

Objectives: To compare the infection rate in patients who underwent carpal tunnel surgery with and without instilling local antibiotics into the surgical wound. METHODS: The retrospective cohort study was conducted at the Department of Surgery, Unit of Neurosurgery, Government Naseer Ullah Babar Memorial Hospital, Peshawar, Pakistan, and comprised data from July 2019 to July 2021 related to non-diabetic patients without any comorbidity who had undergone fresh carpal tunnel surgery. The cases had been operated by two surgeons having a different approach to preventing infection in carpal tunnel surgery cases. The surgeon in group A did not use any local antibiotics after completing the surgery, while the surgeon in group B instilled local gentamicin in the open wound for 3 minutes after completing the nerve release. All patients were put on oral antibiotics for a period of 5 days after the procedure in both the cohorts, and were assessed fortnightly for any infection and removal of stitches. Demographics of the patients, use of antibiotics and the occurrence of infection were recorded on a proforma. Data was analysed using SPSS 20. RESULTS: Of the 177 patients operated during the period, 13(7.3%) were discarded owing to missing data. Of the 164(92.7%) patients analysed, 138(84.14%) were females and 26(15.85%) were males. The overall mean age was 32.46±8.97 years. The total surgeries conducted were 176; 96(54.54%) in group A and 80(45.45%) in group B. Infections were found in 3(1.7%) patients; all in group A (p=0.160). CONCLUSIONS: Although not statistically significant, instillation of local antibiotics may play a role in preventing surgical site infections in carpal tunnel surgery cases.

Efficacy of professionally administered chemical agents as an adjunctive treatment to sub-marginal instrumentation during the therapy of peri-implant mucositis.

AIM: To evaluate the efficacy of professionally administered chemical agents as an adjunctive treatment to sub-marginal instrumentation (SMI) in the therapy of peri-implant mucositis. MATERIALS AND METHODS: The primary outcome criteria were reduction in bleeding on probing (BOP), whereas resolution of disease, elimination of suppuration, including suppuration on probing, reduction of peri-implant probing pocket depth, reduction of plaque, and patient-reported outcome measures were considered as secondary outcome parameters. A literature search was performed on three electronic databases (01/1980 to 05/2022) focused on clinical studies with at least 3 months of follow-up, and meta-analyses were performed when appropriate. RESULTS: From a total of 139 publications, 40 articles were identified for full-text reading, and 5 randomized controlled clinical trials (RCTs) on antimicrobial photodynamic therapy (aPDT), 1 RCT on chlorhexidine (CHX), and 1 RCT on sodium hypochlorite (NaOCl) were included. Three studies had a low risk of bias and four had a mid-level (some concerns) risk of bias. The application of aPDT, 0.95% NaOCl, or 0.12% CHX as an adjunctive treatment to SMI showed no difference in changes in BOP and PD compared with SMI alone (p > .05). CONCLUSIONS: Within the limitations of this review and based on a low level of evidence from seven RCTs, it is concluded that the professional adjunctive topical application of aPDT, 0.95% NaOCl, and 0.12% CHX may not be effective to improve changes for BOP and PD when compared with SMI alone.

Use of Antimicrobial Irrigation and Incidence of Capsular Contracture in Breast Augmentation and Immediate Implant-Based Breast Reconstruction.

Capsular contracture (CC) is one of the most common complications of implant-based breast reconstruction or augmentation surgery. Common risk factors of CC include biofilm, surgical site infections, history of prior CC or fibrosis, history of radiation therapy, and implant characteristics. Though bacterial contamination of breast protheses is associated with adverse sequelae, there are not universally accepted guidelines and limited best practice recommendations for antimicrobial breast pocket irrigation. Despite advanced molecular biology, the exact mechanism of this complication is not fully understood. Interventions that decrease the rate of CC include antibiotic prophylaxis or irrigation, acellular dermal matrix, leukotriene inhibitors, surgical techniques, and others. However, there is inconsistent evidence supporting these risk factors, and the current data was based on broad heterogeneous studies. The objective of this review was to provide a summary of the current data of contributing risk factors as well as preventative and treatment measures for CC.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Antibiotics versus non-antibiotic treatments for acute otitis externa: A systematic review and meta-analysis.

BACKGROUND: Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics. This systematic review and meta-analysis of randomised controlled trials aims to assess the effectiveness of topical non-antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa. METHODS: Systematic review and meta-analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non-antibiotic agents in adults and children with acute otitis externa. Non-antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non-pharmaceuticals and astringents. RESULTS: Seventeen trials were eligible for inclusion, with 10 combined in meta-analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta-analysis. CONCLUSION: Antiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.

Topical Nanotherapeutics for Treating MRSA-Associated Skin and Soft Tissue Infection (SSTIs).

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) imposes a major challenge for the treatment of infectious diseases with existing antibiotics. MRSA associated with superficial skin and soft tissue infections (SSTIs) is one of them, affecting the skin's superficial layers, and it includes impetigo, folliculitis, cellulitis, furuncles, abscesses, surgical site infections, etc. The efficient care of superficial SSTIs caused by MRSA necessitates local administration of antibiotics, because oral antibiotics does not produce the required concentration at the local site. The topical administration of nanocarriers has been emerging in the area of drug delivery due to its advantages over conventional topical formulation. It enhances the solubility and permeation of the antibiotics into deeper layer of the skin. Apart from this, antibiotic resistance is something that needs to be combated on multiple fronts, and antibiotics encapsulated in nanocarriers help to do so by increasing the therapeutic efficacy in a number of different ways. The current review provides an overview of the resistance mechanism in S. aureus as well as various nanocarriers reported for the effective management of MRSA-associated superficial SSTIs.

Review of the current antibiotic guidelines used in dermatologic surgery.

Antibiotics have been used as a prophylaxis for dermatologic procedures. We will review the various procedures that specific antibiotics with dosages are used for, depending on the procedure, diagnosis, and circumstance of the patient. We will examine the current and updated guidelines used in dermatologic surgery and the overlapping guidelines across other fields. Physicians must consider the side effects of antibiotics and the resistance that may occur as a result before using the class or level of prophylaxis. Initial evaluation for alcohol, chlorhexidine, or iodine should be measured as well. Updated guidelines aim to address the contraindications of antibiotics, yet further research is needed to avoid antibiotic resistance and to explore alternative methods of antibiotic application, such as intranasal and intravenous.

Management of Endophthalmitis with and without Topical Antibiotics: A Case-Control Study.

PURPOSE: The aim of this study was to compare the management outcome of endophthalmitis with and without the use of topical antibiotics. METHODS: A retrospective comparative chart review of 2 cohorts of endophthalmitis (other than those associated with open-globe injury, keratitis, or wound site infection), one managed with topical antibiotics (TA group) and one without (NTA group), was performed. RESULTS: The study included a total of 270 eyes of 270 patients. Of these, 169 eyes were in the TA group and 101 were in the NTA group. Post-cataract surgery was the most common etiology, accounting for 81.06 and 78.2% of cases, respectively (p = 0.57). A favorable functional outcome at the last visit was seen in 37.5 and 39.6% of eyes (p = 0.73), and a favorable anatomic outcome was noted in 61.2 and 49.5% of eyes (p = 0.06), respectively. The median follow-up was 3.5 and 9 months, respectively (p < 0.0001). Susceptibilities to the common antibiotics used (vancomycin, ceftazidime, and amikacin) were comparable, with the exception of imipenem, for which the susceptibility noted was 95 and 66%, respectively (p = 0.01). Culture positivity in the TA group was seen in 72 out of 169 eyes (42.6%), while in the NTA group it was seen in 98 out of 101 eyes (97.02%; p < 0.0001). CONCLUSION: Topical antibiotics do not give any added advantage in the management of endophthalmitis otherwise being treated with intravitreal antibiotics and standard vitrectomy techniques.

Outcome of Irrigation and Debridement With Topical Antibiotics Delivery for the Management of Periprosthetic Joint Infection Occurring Within 3 Months Since the Primary Total Joint Arthroplasty.

BACKGROUND: Irrigation and debridement with modular component exchange is appealing for surgeons to treat early-stage periprosthetic joint infection (PJI). However, the indication, perioperative protocol, and success rate remain controversial. This study is the first one to present results of debridement, antibiotics, and implant retention (DAIR) with integrated MIT (modular component exchange, povidone-iodine and topical antibiotics delivery) protocol for treating PJI occurring within 3 months since the primary total joint arthroplasty. METHODS: We retrospectively analyzed patients who received DAIR with MIT protocol in our department between January 2011 and May 2018. Topical antibiotics were delivered in all cases. Topical antibiotics infusion was applied for those infected with multidrug-resistant bacteria, fungus, polymicrobial infection, and culture negative one. Failure was defined as additional surgical intervention for infection after DAIR; persistent sinus tract, drainage or excessive joint pain; need for suppressive antibiotics therapy due to the infection; infection relapse with the same pathogen; reinfection with different microorganism; and infection-related death. RESULTS: A total of 73 patients with a mean age of 63.30 ± 10.97 years were included in this study, including 43 men and 30 women. There are 41 knees and 32 hips. Thirty patients had sinus tract. With a mean follow-up of 63.79 ± 18.57 months, there were 9 failures in total with an overall success rate of 87.67%. The success rate was 88.57% and 86.84% for those receiving topical antibiotics infusion postoperatively and those without. CONCLUSIONS: DAIR with a standard MIT protocol is a viable and safe option for PJI occurring within 3 months since the primary total joint arthroplasty. LEVEL OF EVIDENCE: Level 4, therapeutic study.

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro.

Chronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of a therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 h at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells. The antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

Ozenoxacin, a New Effective and Safe Topical Treatment for Impetigo in Children and Adolescents.

BACKGROUND: Ozenoxacin is a topical antibiotic approved in Europe to treat non-bullous impetigo in adults and children aged ≥6 months. This analysis evaluated the efficacy and safety of ozenoxacin in paediatric patients by age group. METHODS: Pooled data for patients aged 6 months to <18 years who had participated in a phase I or in two phase III clinical trials of ozenoxacin 1% cream were analysed by age group: 0.5-<2, 2-<6, 6-<12, and 12-<18 years. RESULTS: The combined population comprised 529 patients with non-bullous impetigo treated with ozenoxacin (n = 239), vehicle (n = 201), or retapamulin as internal validation control (n = 89). Studies were well matched for extent and severity of impetigo and therapeutic schedule (twice daily application for 5 days). The clinical success rate after 5 days' treatment (day 6-7, end of therapy), and microbiological success rates after 3-4 days' treatment and at the end of therapy, were significantly higher with ozenoxacin than vehicle (p < 0.0001 for all comparisons). Clinical and bacterial eradication rates were higher with ozenoxacin than vehicle in each age group. No safety concerns were identified with ozenoxacin. One (0.3%) of 327 plasma samples exceeded the lower limit of quantification for ozenoxacin, but the low concentration indicated negligible systemic absorption. CONCLUSION: This combined analysis supports the efficacy and safety of ozenoxacin administered twice daily for 5 days. Ozenoxacin 1% cream is a new option to consider for treatment of non-bullous impetigo in children aged 6 months to <18 years.

Antibacterial effects of antibiotics and cell-free preparations of probiotics against Staphylococcus aureus and Staphylococcus epidermidis associated with conjunctivitis.

Conjunctivitis, caused by bacterial infections, represents health concern and diagnosis of the disease is pivotal for the proper selection of the treatment. The main causes of bacterial conjunctivitis vary in different countries. The current study investigated the common bacterial causes of bacterial conjunctivitis from eye clinics' attendants and evaluated the effectiveness of different therapeutic approaches. Eye swabs from patients, diagnosed with conjunctivitis, were assessed microbiologically and the isolated bacteria were identified using the standard biochemical identification and sequencing of the 16S rRNA gene. Antibiotics' susceptibility of the conjunctivitis-associated bacterial pathogens was evaluated against nineteen broad-spectrum antibiotics. In the meanwhile, cell-free preparations from probiotic Lactobacillus and Bifidobacterium strains were used to evaluate their antagonistic activities. Findings from this study showed that out of 52 specimen, 17 eye swabs from patients with conjunctivitis were bacterial culture-positive. The identity of the bacterial species, using the biochemical identification system, was Staphylococcus aureus (4 isolates) and S. epidermidis (13 isolates). Staphylococcus spp. showed susceptibility to linezolid, vancomycin, novobiocin, and fluoroquinolones (norfloxacin, ofloxacin, ciprofloxacin and levofloxacin). However, isolates from the two Staphylococcus spp. expressed resistance to penicillin G, oxacillin, and cephalexin. As alternatives to antibiotics, the growth of Staphylococcus spp., including isolates with antibiotic resistance, was inhibited by cell-free preparations of the 4 probiotic Lactobacillus and the 2 Bifidobacterium strains. These findings provide evidence that topical antibiotics such as fluoroquinolones are still effective antimicrobial agents against staphylococci associated with conjunctivitis whereas probiotic preparations could be promising for further research to pave the way for their therapeutic applications against ophthalmic diseases.

Cutibacterium acnes persists despite topical clindamycin and benzoyl peroxide.

BACKGROUND: Cutibacterium (formerly Propionibacterium) acnes persists in the dermis despite standard skin antiseptic agents, prompting some surgeons to use topical antimicrobials such as benzoyl peroxide and clindamycin prior to shoulder arthroplasty surgery. However, the efficacy of these topical agents has not been established. METHODS: The upper backs of 12 volunteers were randomized into 4 treatment quadrants: topical benzoyl peroxide, topical clindamycin, combination topical benzoyl peroxide and clindamycin, and a negative control. The corresponding topical agents were applied to each site twice daily for 3 days. A 3-mm dermal punch biopsy specimen was obtained from each site and cultured for 14 days to assess for C acnes growth. Positive cultures were assessed for the hemolytic phenotype. The McNemar test was used to compare the proportion of positive cultures in each group. RESULTS: C acnes grew in 4 of 12 control sites (33.3%), 1 of 12 benzoyl peroxide sites (8.3%), 2 of 12 clindamycin sites (16.7%), and 2 of 12 combination benzoyl peroxide-clindamycin sites (16.7%). The C acnes hemolytic phenotype was present in 2 of 12 control specimens (16.7%) compared with 0 (0.0%) in the benzoyl peroxide group, 2 of 12 (16.7%) in the clindamycin group, and 2 of 12 (16.7%) in the combination benzoyl peroxide-clindamycin group. There were no statistically significant differences between treatment arms. CONCLUSION: The topical application of benzoyl peroxide and clindamycin did not eradicate C acnes in all subjects. The clinical implications of these findings are yet to be determined.

Systematic Review and Meta-Analysis of Intrawound Vancomycin in Total Hip and Total Knee Arthroplasty: A Call for a Prospective Randomized Trial.

BACKGROUND: Topical intrawound vancomycin has been used extensively in spine surgery to decrease surgical site infections. However, the efficacy of intrawound vancomycin in total hip (THA) and total knee arthroplasty (TKA) to prevent periprosthetic joint infection (PJI) has not been established. METHODS: The PubMed and MEDLINE databases were searched to identify studies utilizing intrawound vancomycin in primary and revision THA and TKA. Data for postoperative infection were pooled using random effect models with results reported as odds ratios (ORs) and 95% confidence intervals. Studies were weighted by the inverse variance of their effect estimates. RESULTS: Of the 91 studies identified, 6 low-quality retrospective studies (level III) were pooled for further analysis. A total of 3298 patients were assessed, 1801 of which were treated with intrawound vancomycin. Overall, patients who received vancomycin had a decreased rate of PJI (OR 0.2530, P < .0001). When analyzed separately, TKA patients and THA patients who received intrawound vancomycin had lower rates of PJI (OR 0.3467, P = .0005 and OR 0.3672, P = .0072, respectively). Pooled primary TKA and THA patients receiving vancomycin saw the rate of PJI decrease (OR 0.4435, P = .0046). Pooled revision TKA and THA patients saw a similar decrease in infection rates (OR 0.2818, P = .0013). No apparent publication bias was observed; however, the results from this analysis are limited by the low quality of evidence and inherent potential for bias. CONCLUSION: Intrawound vancomycin may reduce the risk of PJI in primary and revision TKA and THA. However, only low-quality evidence exists, highlighting the need for randomized controlled trials before broad adoption of this practice can be recommended given the potential implications of widespread use of vancomycin in hip and knee arthroplasty.

Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus.

Topical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) community Staphylococcus aureus isolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1 S. aureus We also provide in vitro experimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDR S. aureus isolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.

In vitro antibacterial effects of statins against bacterial pathogens causing skin infections.

With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins' antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 µg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli, P. aeruginosa, or S. marcescens, but simvastatin hydroxy acid acid might be active against S. aureus, E. coli, and S. marcescens at drug concentrations > 256 µg/mL. It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins' antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.

Topical Polymyxin-Trimethoprim Prophylaxis May Decrease the Incidence of Driveline Infections in Patients With Continuous-Flow Left Ventricular Assist Devices.

This retrospective cohort study evaluated the effect of topical polymyxin-trimethoprim (poly) prophylaxis on the incidence of driveline infections (DLIs) in patients with continuous-flow left ventricular assist devices. All 84 cases implanted 2005-2014 with device support ≥30 days were reviewed; support ranged 1 m-5.2 yrs. Beginning 2008, poly was applied to the exit site with dressing changes. Sixty-five patients received poly (poly group) for duration of follow-up, 19 did not (no-poly); group baseline characteristics were similar. No patient developed side effects from poly. Nineteen DLIs (10 in no-poly) occurred; not using poly was a risk factor. 89% of poly group DLIs were superficial, 4 were culture-negative. DLI-related bacteremia occurred in 11% of no-poly group and 0% of poly group. Compared with no-poly, poly group demonstrated improved freedom from DLI by Kaplan-Meier analysis (P < 0.0001) and a 75% lower overall and 95% lower deep DLI incidence (P ≤ 0.001). Deep DLIs occurred in 31.6% of no-poly vs. 1.5% of poly patients (P = 0.0004), although mean support duration (1 yr) and % support >1 yr (38%) were similar. These findings, which should be confirmed with larger comparative studies, suggest that topical polymyxin-trimethoprim prophylaxis may be effective in preventing DLIs.

Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro.

BACKGROUND AND OBJECTIVES: Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy. STUDY DESIGN/MATERIALS AND METHODS: Staphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 µg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay. RESULTS: With gentamicin monotherapy, CFU density (CFU/mm2 ) at 31, 62, and 124 µg/ml were (282 ± 84) × 104 , (185 ± 34) × 104 , and (113 ± 9) × 104 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 104 , (89 ± 24) × 104 , and (43 ± 3) × 104 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 µg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities. CONCLUSION: LGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc.