Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.

Patient compliance with the implementation of a decolonization strategy for Staphylococcus aureus in hip and knee replacements.

BACKGROUND: A preoperative, in-community antimicrobial decolonization protocol combining chlorohexidine gluconate (CHG) sponges and mupirocin ointment to reduce surgical site infections amongst hip and knee replacement patients has been adopted in Alberta, Canada. Patient compliance with the protocol is essential for effectiveness. It is, therefore, important to understand patterns, and reasons why, patients do, and do not, comply. METHODS: A descriptive survey of patients having elective total hip or knee replacement at seven clinics in Alberta was conducted to determine patient compliance and reasons for noncompliance. Descriptive statistics and multivariate logistic regression were computed. RESULTS: Patient compliance was assessed in 3,427 patients. There were no differences in compliance based on the baseline protocols and enhanced protocols, but there was a difference based on clinic location. The odds of compliance with three CHG sponges were 4.47 times higher in rural versus urban clinics (P < .001). The most common reason for noncompliance for patients instructed to use 3 CHG sponges was "patient forgot". CONCLUSIONS: Compliance did not change when enhanced protocols were introduced; however, compliance differed by clinic location. Reasons for noncompliance included "sponges not provided", "patient forgot", and "surgery date moved". Results may inform clinics on areas where improvements could be made to increase patient compliance.

Topical antibiotics prophylaxis for infections of indwelling pleural/peritoneal catheters (TAP-IPC): A pilot study.

BACKGROUND AND OBJECTIVE: Indwelling pleural catheter (IPC) and indwelling peritoneal catheter (IPeC) have established roles in the management of malignant pleural and peritoneal effusions but catheter-related infections remain a major concern. Topical mupirocin prophylaxis has been shown to reduce peritoneal dialysis catheter infections. This study aimed to assess the (i) compatibility of IPC with mupirocin and (ii) feasibility, tolerability and compliance of topical mupirocin prophylaxis in patients with an IPC or IPeC. METHODS: (i) Three preparations of mupirocin were applied onto segments of IPC thrice weekly and examined with scanning electron microscope (SEM) at different time intervals. (ii) Consecutive patients fitted with IPC or IPeC were given topical mupirocin prophylaxis to apply to the catheter exit-site following every drainage/dressing change (at least twice weekly) and followed up for 6 months. RESULTS: (i) No detectable structural catheter damage was found with mupirocin applied for up to 6 months. (ii) Fifty indwelling catheters were inserted in 48 patients for malignant pleural (n = 41) and peritoneal (n = 9) effusions. Median follow-up was 121 [median, IQR 19-181] days. All patients tolerated mupirocin well; one patient reported short-term local tenderness. Compliance was excellent with 95.8% of the 989 scheduled doses delivered. Six patients developed catheter-related pleural (n = 3), concurrent peritoneal/local (n = 1) and skin/tract (n = 2) infections from Streptococcus mitis (with Bacillus species or anaerobes), Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. CONCLUSION: This first study of long-term prevention of IPC- or IPeC-related infections found topical mupirocin prophylaxis feasible and well tolerated. Its efficacy warrants future randomized studies.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

Nasal decolonization: What antimicrobials and antiseptics are most effective before surgery and in the ICU.

BACKGROUND: Staphylococcus aureus colonization is a key risk factor for S. aureus infections in surgical patients and in hospitalized patients. Many studies have assessed various decolonization agents, protocols, and settings. This review summarizes key findings about nasal decolonization for 2 different patient populations: patients undergoing surgery and patients hospitalized in intensive care units. METHODS: We reviewed major studies related to decolonization of patients colonized with S. aureus and who were either undergoing surgical procedures or were hospitalized in intensive care units. We focused on recent studies, particularly randomized controlled trials and robust quasi-experimental trials. We also reviewed select non-randomized trials when more rigorous trials were limited. DISCUSSION/CONCLUSIONS: Mupirocin is the best-studied agent for decolonization. Its use reduces the risk of surgical site infection following orthopedic surgery (strongest data) and cardiac surgery. Mupirocin decolonization also reduces the incidence of S. aureus clinical cultures in the intensive care unit. Povidone-iodine is less well-studied. Current data suggest that it decreases the risk of surgical site infections after orthopedic surgical procedures. In contrast, povidone-iodine is less effective than mupirocin for reducing the incidence of S aureus clinical cultures in the intensive care unit. Both mupirocin and povidone-iodine have important limitations, highlighting the need for future decolonization research.

Bacterial Decolonization for Prevention of Radiation Dermatitis: A Randomized Clinical Trial.

Importance: Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care. Objective: To determine the efficacy of bacterial decolonization (BD) to reduce ARD severity compared with standard of care. Design, Setting, and Participants: This phase 2/3 randomized clinical trial was conducted from June 2019 to August 2021 with investigator blinding at an urban academic cancer center and enrolled patients with breast cancer or head and neck cancer receiving radiation therapy (RT) with curative intent. Analysis was performed on January 7, 2022. Interventions: Intranasal mupirocin ointment twice daily and chlorhexidine body cleanser once daily for 5 days prior to RT and repeated for 5 days every 2 weeks through RT. Main Outcomes and Measures: The primary outcome as planned prior to data collection was the development of grade 2 or higher ARD. Based on wide clinical variability of grade 2 ARD, this was refined to grade 2 ARD with moist desquamation (grade 2-MD). Results: Of 123 patients assessed for eligibility via convenience sampling, 3 were excluded, and 40 refused to participate, with 80 patients in our final volunteer sample. Of 77 patients with cancer (75 patients with breast cancer [97.4%] and 2 patients with head and neck cancer [2.6%]) who completed RT, 39 were randomly assigned BC, and 38 were randomly assigned standard of care; the mean (SD) age of the patients was 59.9 (11.9) years, and 75 (97.4%) were female. Most patients were Black (33.7% [n = 26]) or Hispanic (32.5% [n = 25]). Among patients with breast cancer and patients with head and neck cancer (N = 77), none of the 39 patients treated with BD and 9 of the 38 patients (23.7%) treated with standard of care developed ARD grade 2-MD or higher (P = .001). Similar results were observed among the 75 patients with breast cancer (ie, none treated with BD and 8 [21.6%] receiving standard of care developed ARD grade ≥2-MD; P = .002). The mean (SD) ARD grade was significantly lower for patients treated with BD (1.2 [0.7]) compared with patients receiving standard of care (1.6 [0.8]) (P = .02). Of the 39 patients randomly assigned to BD, 27 (69.2%) reported regimen adherence, and only 1 patient (2.5%) experienced an adverse event related to BD (ie, itch). Conclusions and Relevance: The results of this randomized clinical trial suggest that BD is effective for ARD prophylaxis, specifically for patients with breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03883828.

Exploiting Broad-Spectrum Chimeric Lysin to Cooperate with Mupirocin against Staphylococcus aureus-Induced Skin Infections and Delay the Development of Mupirocin Resistance.

Staphylococcus aureus often leads to severe skin infections. However, S. aureus is facing a crisis of antibiotic resistance. The combination of phage and antibiotics is effective for drug-resistant S. aureus infections. Therefore, it is worth exploiting novel antibacterial agents to cooperate with antibiotics against S. aureus infections. Herein, a novel chimeric lysin ClyQ was constructed, which was composed of a cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) catalytic domain from S. aureus phage lysin LysGH15 and cell wall-binding domain (CBD) from Enterococcus faecalis phage lysin PlyV12. ClyQ had an exceptionally broad host range targeting streptococci, staphylococci, E. faecalis, and E. rhusiopathiae. ClyQ combined with mupirocin (2.64 log reduction) was more effective at treating S. aureus skin infections than ClyQ (0.46 log reduction) and mupirocin (2.23 log reduction) alone. Of equal importance, none of S. aureus ATCC 29213 or S3 exposed to ClyQ developed resistance, and the combination of ClyQ and mupirocin delayed the development of mupirocin resistance. Collectively, chimeric lysin ClyQ enriches the reservoirs for treating S. aureus infections. Our findings may provide a way to alleviate the current antibiotic resistance crisis. IMPORTANCE Staphylococcus aureus, as an Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogen, can escape the elimination of existing antibiotics. At present, phages and phage lysins against S. aureus infections are considered alternative antibacterial agents. However, the development of broad-spectrum chimeric phage lysins to cooperate with antibiotics against S. aureus infections remains at its initial stage. In this study, we found that the broad-host-range chimeric lysin ClyQ can synergize with mupirocin to treat S. aureus skin infections. Furthermore, the development of S. aureus resistance to mupirocin is delayed by the combination of ClyQ and mupirocin in vitro. Our results bring research attention toward the development of chimeric lysin that cooperates with antibiotics to overcome bacterial infections.

Effectiveness and acceptability of intranasal povidone-iodine decolonization among fracture fixation surgery patients to reduce Staphylococcus aureus nasal colonization.

We evaluated povidone-iodine (PVI) decolonization among 51 fracture-fixation surgery patients. PVI was applied twice on the day of surgery. Patients were tested for S. aureus nasal colonization and surveyed. Mean S. aureus concentrations decreased from 3.13 to 1.15 CFU/mL (P = .03). Also, 86% of patients stated that they felt neutral or positive about their PVI experience.

Pre-surgical Nasal Decolonization of Staphylococcus aureus: A Health Technology Assessment.

Background: Staphylococcus aureus (S. aureus) is the most common cause of surgical site infections, and the nose is the most common site for S. aureus colonization. Pre-surgical (in the days prior to surgery) nasal decolonization of S. aureus may reduce the bacterial load and prevent the organisms from being transferred to the surgical site, thus reducing the risk of surgical site infection. We conducted a health technology assessment of nasal decolonization of S. aureus (including methicillin-susceptible and methicillin-resistant strains) with or without topical antiseptic body wash to prevent surgical site infection in patients undergoing scheduled surgery, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding nasal decolonization of S. aureus, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews and selected and reported results from one review that was recent, of high quality, and relevant to our research question. We complemented the chosen systematic review with a literature search to identify randomized controlled trials published since the systematic review was published in 2019. We used the Risk of Bias in Systematic Reviews (ROBIS) tool to assess the risk of bias of each included systematic review and the Cochrane risk-of-bias tool for randomized controlled trials to assess the risk of bias of each included primary study. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted both cost-effectiveness and cost-utility analyses using a decision-tree model with a 1-year time horizon from the perspective of Ontario's Ministry of Health. We also analyzed the budget impact of publicly funding nasal decolonization of S. aureus in pre-surgical patients in Ontario. To contextualize the potential value of nasal decolonization, we spoke with people who had recently undergone surgery, some of whom had received nasal decolonization, and one family member of a person who had recently had surgery. We also engaged participants through an online survey. Results: We included one systematic review and three randomized controlled trials in the clinical evidence review. In universal decolonization, compared with placebo or no intervention, nasal mupirocin alone may result in little to no difference in the incidence of overall and S. aureus-related surgical site infections in pre-surgical patients undergoing orthopaedic, cardiothoracic, general, oncologic, gynaecologic, neurologic, or abdominal digestive surgeries, regardless of S. aureus carrier status (GRADE: Moderate to Very low). Compared with placebo, nasal mupirocin alone may result in little to no difference in the incidence of overall and S. aureus-related surgical site infections in pre-surgical patients who are S. aureus carriers undergoing cardiothoracic, vascular, orthopaedic, gastrointestinal, general, oncologic, gynaecologic, or neurologic surgery (GRADE: Moderate to Very low). In targeted decolonization, compared with placebo, nasal mupirocin combined with chlorhexidine body wash lowers the incidence of S. aureus-related surgical site infection (risk ratio: 0.32 [95% confidence interval: 0.16-0.62]) in pre-surgical patients who are S. aureus carriers undergoing cardiothoracic, vascular, orthopaedic, gastrointestinal, or general surgery (GRADE: High). Compared with no intervention, nasal mupirocin combined with chlorhexidine body wash in pre-surgical patients who are not S. aureus carriers undergoing orthopaedic surgery may have little to no effect on overall surgical site infection, but the evidence is very uncertain (GRADE: Very low). Most included studies did not separate methicillin-susceptible and methicillin-resistant strains of S. aureus. No significant antimicrobial resistance was identified in the evidence reviewed; however, the existing literature was not adequately powered and did not have sufficient follow-up time to evaluate antimicrobial resistance.Our economic evaluation found that universal nasal decolonization using mupirocin combined with chlorhexidine body wash is less costly and more effective than both targeted and no nasal decolonization. Compared with no nasal decolonization treatment, universal and targeted nasal decolonization using mupirocin combined with chlorhexidine body wash would prevent 32 and 22 S. aureus-related surgical site infections, respectively, per 10,000 patients. Universal nasal decolonization would lead to cost savings, whereas targeted nasal decolonization would increase the overall cost for the health care system since patients must first be screened for S. aureus carrier status before receiving nasal decolonization with mupirocin. The annual budget impact of publicly funding universal nasal decolonization in Ontario over the next 5 years ranges from a savings of $2.98 million in year 1 to a savings of $15.09 million in year 5. The annual budget impact of publicly funding targeted nasal decolonization ranges from an additional cost of $0.08 million in year 1 to an additional cost of $0.39 million in year 5.Our interview and survey respondents felt strongly about the value of preventing surgical site infections, and most favoured a universal approach. Conclusions: Based on the best evidence available, decolonization of S. aureus using nasal mupirocin combined with chlorhexidine body wash prior to cardiothoracic, vascular, orthopaedic, gastrointestinal, or general surgery lowers the incidence of surgical site infection caused by S. aureus in patients who are S. aureus carriers (including methicillin-susceptible and methicillin-resistant strains) (i.e., targeted decolonization). However, nasal mupirocin alone may result in little to no difference in overall surgical site infections and S. aureus-related surgical site infections in pre-surgical patients prior to orthopaedic, cardiothoracic, general, oncologic, gynaecologic, neurologic, or abdominal digestive surgeries, regardless of their S. aureus carrier status (i.e., universal decolonization). No significant antimicrobial resistance was identified in the evidence reviewed.Compared with no nasal decolonization treatment, universal nasal decolonization with mupirocin combined with chlorhexidine body wash may reduce S. aureus-related surgical site infections and lead to cost savings. Targeted nasal decolonization with mupirocin combined with chlorhexidine body wash may also reduce S. aureus-related surgical site infections but increase the overall cost of treatment for the health care system. We estimate that publicly funding universal nasal decolonization using mupirocin combined with chlorhexidine body wash would result in a total cost savings of $45.08 million over the next 5 years, whereas publicly funding targeted nasal decolonization using mupirocin combined with chlorhexidine body wash would incur an additional cost of $1.17 million over the next 5 years.People undergoing surgery value treatments aimed at preventing surgical site infections.

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model.

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.

Accelerative effect of nanohydrogels based on chitosan/ZnO incorporated with citral to heal the infected full-thickness wounds; an experimental study.

Antimicrobial-resistant is a major challenge in to treat infected wounds, and new formulations should be produced. Citral (Citl), chitosan (Chsn), and zinc oxide (ZnO) nanoparticles may accelerate the wound healing process in terms of their antibacterial properties. This new study aimed to investigate the effects of ointments produced from ZnO/Chsn/Citl nanoparticles (NPs) to treat the infected wounds. Following the preparation of ZnO/Chsn/Citl-NPs, swelling behavior, the release of citral, toxicity, and antibacterial properties were evaluated. Base ointment, mupirocin, and ointments made from Chsn-NPs, Chsn/Citl-NPs, and ZnO/Chsn/Citl-NPs were used to treat the mice. The ointments' effects on wound contraction, total bacterial count, and immunofluorescence staining for TNF-α, TGF-ß, and bFGF were tested. The synthesis of ZnO/Chsn/Citl-NPs was validated by XRD, FT-IR, DLS, and TEM findings. In higher dilutions, chitosan/citral and ZnO/Chsn/Citl-NPs indicated better antibacterial activity. Nanoparticles were safe up to concentration of the 0.5 mg/mL. The mice in Chsn/Citl and ZnO/Chsn/Citl-NPs treated groups showed higher (P < 0.05) wound contraction ratio and expressions for bFGF, and lower total bacterial count and expressions for TGF-ß and TNF-α compared to control mice. Ointments prepared from ZnO/Chsn/Citl-NPs could compete with the commercial ointment of mupirocin and can be used to treat infected wounds after clinical studies.

Attitudes and Awareness of Cornea Specialists and Oculoplastic Surgeons toward Methicillin-Resistant Staphylococcus aureus Decolonization.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is widely utilized in many medical subspecialities to reduce surgical site infections, but routine ophthalmic implementation has been limited. The aim of this study was to investigate the attitudes and actual practice of corneal specialists and oculoplastic surgeons toward MRSA decolonization as a preventive measure in ophthalmic surgery. Materials and Methods: A web-based survey was sent to cornea specialists and oculoplastic surgeons to assess their knowledge, beliefs, and practices regarding MRSA prophylaxis and the use of MRSA decolonization to prevent post-operative infections. Results: A total of 180 surgeons participated in this study: 71% of respondents agreed that MRSA colonization plays a role in post-operative infection of the eye and adnexal structures; 65% stated that MRSA decolonization could help prevent MRSA infection. Although 41% of respondents would change their management in response to a positive pre-operative MRSA screening result, only 18% performed pre-operative screening. Seventeen percent of respondents indicated that they offer pre-operative decolonization for MRSA-positive patients; the most frequently applied technique was the use of nasal antibiotic agents such as mupirocin, followed by antiseptic baths. Peri-operative MRSA prophylaxis was used by 18% of respondents; pre-operative MRSA decolonization was used in conjunction by 8.5 % of respondents. Conclusions: Although MRSA decolonization has been validated in fields outside of ophthalmology, there has not been widespread adoption of this practice among oculoplastic surgeons and cornea specialists. Prospective MRSA decolonization ophthalmic studies are necessary if evidence-based management guidelines are to be developed.

Choose Your Patients Wisely: A Preoperative Protocol to Reduce Surgical Site Infection Rates in Elective Neurosurgical Procedures.

OBJECTIVE: Surgical site infections (SSIs) are the most common and costly of all hospital-acquired infections, occurring in 5 percent of patients and accounting for 20% of all hospital-acquired infections. Preoperatively, we developed a protocol where patients were screened using hemoglobin A 1c (HbA1c) and nasal swabs. If HbA1c was greater than 9, patients were rescheduled for surgery when their HbA1c was less than 9. All patients then underwent nasal swabs to identify methicillin-sensitive Staphylococcus aureus/methicillin-resistant S. aureus in addition to standard chlorhexidine gluconate bathing. If positive, mupirocin ointment was used to treat the patients 5 days prior to surgery. We sought to measure the effectiveness of this protocol in reducing SSI in elective neurosurgical patients who were undergoing hardware implantation or had a procedure anticipated to last greater than 2 hours. METHODS: This was a retrospective review of patients undergoing elective neurosurgical procedures at Conemaugh Memorial Medical Center from 1/1/2014 to 06/30/2016. The intervention period was from 7/1/2016 to 12/20/2018, which included the patients undergoing the protocol. RESULTS: The preintervention group consisted of 817 cases with a 2.7% infection rate (22 SSIs). The intervention group consisted of 822 cases with a 0.1% infection rate (1 SSI). This observed difference was statistically significant (P = 0.003). CONCLUSIONS: This retrospective review of a presurgical protocol with measuring of HbA1c and nasal swabs revealed a significant decrease in the infection rate of patients undergoing elective neurosurgical procedures. Additional investigations are necessary; however, we recommend its use.

Lowbury Lecture 2021: tales of the unexpected in antibiotic resistance.

Since the 1990s few new antibiotics have become available; during the same period the appearance and spread of bacteria no longer susceptible to first- and second-line antibiotics has accelerated; indeed some bacterial infections have become untreatable with existing antibiotics. Control of antibiotic resistance is multifactorial, and includes restrictive antibiotic use and good infection control. This lecture addresses three aspects of antibiotic resistance, with reference to the Netherlands, that illustrate the complexity of antibiotic resistance epidemiology. Initially selective decontamination of the digestive tract (SDD) was not adopted in the Netherlands because of concern about antibiotic resistance. However, three trials showed that SDD regimens, including four days of systemic cephalosporins, gave better clinical outcomes with no effect on antibiotic-resistant bacteria. Many predictions have been made about the impact of infections with antibiotic-resistant bacteria on human health. However, the situation is complex, because the risk factors for infection with multidrug-resistant bacteria are also risk factors for poor clinical outcome. A study in eight Dutch hospitals estimated the mortality attributable to antibiotic resistance as close to zero. Concern about the emergence of resistance in Staphylococcus aureus has limited the universal use of mupirocin to prevent surgical site infections. However, the risk may have been overstated, and universal decolonization with mupirocin and chlorhexidine has now become standard of care in patients undergoing cardiothoracic or orthopaedic surgery in many Dutch hospitals. Prophylactic antibiotics can improve patient outcomes with acceptable risks of promoting resistance.

Efficacy of mupirocin, neomycin and octenidine for nasal Staphylococcus aureus decolonisation: a retrospective cohort study.

BACKGROUND: Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI. METHODS: Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used. RESULTS: During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452). CONCLUSIONS: Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments.

Nasal screening for methicillin-resistant Staphylococcus aureus does not reduce surgical site infection after primary lumbar fusion.

BACKGROUND CONTEXT: Preoperative methicillin-resistant Staphylococcus aureus (MRSA) testing and decolonization has demonstrated success for arthroplasty patients in surgical site infections (SSIs) prevention. Spine surgery, however, has seen varied results. PURPOSE: The purpose of this study was to determine the impact of nasal MRSA testing and operative debridement rates on surgical site infection after primary lumbar fusion. STUDY DESIGN/SETTING: Retrospective cohort study and/or Consolidated medical enterprise PATIENT SAMPLE: Adult patients undergoing primary instrumented lumbar fusions from January 2015 to December 2019 were reviewed. OUTCOME MEASURES: The primary outcome was incision and drainage performed in the operating room within 90 days of surgery. METHODS: MRSA testing <90-day's before surgery, mupirocin prescription <30-day's before surgery, perioperative antibiotics, and Elixhauser comorbidity index were collected for each subject. Bivariate analysis used Wilcoxon rank-sum testing and logistic regression modeling Multivariable logistic regression modeling assessed for associations with MRSA testing, intravenous vancomycin use, and I&D rate. RESULTS: The study included 1,884 patients for analysis, with mean age of 63.1 (SE 0.3) and BMI 29.5 (SE 0.1). MRSA testing was performed in 755 patients (40.1%) and was more likely to be performed in patients with lower Elixhauser index scores (OR 0.98, 95% CI 0.96-0.99, p=.021) on multivariable analysis. Vancomycin use increased significantly over time (OR 1.49 and/or year, 95% CI 1.3-1.8, p<.001) despite no change in mupirocin or I&D rates. MRSA testing, mupirocin prescriptions, perioperative parenteral vancomycin use, and intrawound vancomycin powder use had no impact on I&D rates. I&D risk was associated with higher BMI (OR 1.06, 95% CI 1.02-1.12, p=.009) and higher number of blood product units transfused (OR 1.23, 95% CI 1.03-1.46, p=.022). CONCLUSIONS: The present study demonstrates no impact on surgical I&D rates from the use of preoperative MRSA testing. Increased BMI and transfusions were associated with operative I&D rates for surgical site infection. As a result of the hospital directive, vancomycin use increased over time with no associated change in infection rates, underscoring the need for focused interventions, and engagement with antibiotic stewardship programs.

Mupirocin ointments: In vitro x In vivo bioequivalence evaluation

Abstract Bioequivalence (BE) assessment of topical drug products is a long-standing challenge. Agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published several drafts in recent years suggesting different approaches as alternative to evaluate the BE. A proposed Topical Classification System (TCS) has even been discussed. Given the above, the objective of this research was to use in vitro and in vivo BE approaches to evaluate Brazilian marketed mupirocin (MPC) ointments, previously classified as TCS class The in vitro permeation test (IVPT) was performed by applying formulations to pig skin by Franz cells. The in vivo methodology was dermatopharmacokinetic (DPK). These approaches (in vivo tape stripping and IVPT) demonstrated capability of distinguishing among different formulations, thus making them useful methodologies for BE evaluation.

Acitretin-induced periungual pyogenic granulomas and review.

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.