Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. Results: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Efficacy of topical cadexomer iodine treatment in chronic wounds: Systematic review and meta-analysis of comparative clinical trials.

The aim of this study was to summarise the clinical evidence supporting almost 40 years of topical cadexomer iodine (CIOD) use in wound bed preparation by removing barriers to healing such as exudate, slough, bioburden, and infection and allowing chronic wound progression. A systematic review was conducted (Embase/PubMed, November 2020) to identify relevant comparative studies meeting inclusion criteria. Meta-analyses were performed using a fixed-effects (I2 < 50%) or random-effects model (I2 ≥ 50%) depending on statistical heterogeneity. Dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD), with 95% confidence intervals. In total, 436 publications were identified of which 13 were comparative trials including outcomes of interest. Significant reductions in exudate, pus/debris, slough, bioburden, and infection were reported in chronic wounds treated with CIOD, compared with standard of care (SOC). Meta-analyses highlighted the positive impact of CIOD on mean wound area reduction (MD = 2.35 cm2 , 95% CI = 0.34-4.36, P = .0219) after eight weeks treatment and overall wound healing events compared to SOC; wounds including venous leg ulcers, diabetic foot ulcers, and pressure ulcers treated with CIOD were more than twice as likely to heal than those receiving SOC (RR = 2.30, 95% CI = 1.54-3.45, P < .0001). This meta-analysis demonstrates the efficacy of CIOD on chronic wounds through removal of barriers to healing. CIOD should be considered in wound bed preparation and treatment protocols.

Evidence-Based Review of Antibiofilm Agents for Wound Care.

Significance: Biofilms in vivo are small densely packed aggregations of microbes that are highly resistant to host immune responses and treatment. They attach to each other and to nearby surfaces. Biofilms are difficult to study and identify in a clinical setting as their quantification necessitates the use of advanced microscopy techniques such as confocal laser scanning microscopy. Nonetheless, it is likely that biofilms contribute to the pathophysiology of chronic skin wounds. Reducing, removing, or preventing biofilms is thus a logical approach to help clinicians heal chronic wounds. Recent Advances: Wound care products have demonstrated varying degrees of efficacy in destroying biofilms in in vitro and preclinical models, as well as in some clinical studies. Critical Issues: Controlled studies exploring the beneficial role of biofilm eradication and its relationship to healing in patients with chronic wounds are limited. This review aims to discuss the mode of action and clinical significance of currently available antibiofilm products, including surfactants, dressings, and others, with a focus on levels of evidence for efficacy in disrupting biofilms and ability to improve wound healing outcomes. Future Directions: Few available products have good evidence to support antibiofilm activity and wound healing benefits. Novel therapeutic strategies are on the horizon. More high-quality clinical studies are needed. The development of noninvasive techniques to quantify biofilms will facilitate increased ease of research about biofilms in wounds and how to combat them.

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections.

Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.

Cluster identification, selection, and description in cluster randomized crossover trials: the PREP-IT trials.

BACKGROUND: In cluster randomized crossover (CRXO) trials, groups of participants (i.e., clusters) are randomly allocated to receive a sequence of interventions over time (i.e., cluster periods). CRXO trials are becoming more comment when they are feasible, as they require fewer clusters than parallel group cluster randomized trials. However, CRXO trials have not been frequently used in orthopedic fracture trials and represent a novel methodological application within the field. To disseminate the early knowledge gained from our experience initiating two cluster randomized crossover trials, we describe our process for the identification and selection of the orthopedic practices (i.e., clusters) participating in the PREP-IT program and present data to describe their key characteristics. METHODS: The PREP-IT program comprises two ongoing pragmatic cluster randomized crossover trials (Aqueous-PREP and PREPARE) which compare the effect of iodophor versus chlorhexidine solutions on surgical site infection and unplanned fracture-related reoperations in patients undergoing operative fracture management. We describe the process we used to identify and select orthopedic practices (clusters) for the PREP-IT trials, along with their characteristics. RESULTS: We identified 58 potential orthopedic practices for inclusion in the PREP-IT trials. After screening each practice for eligibility, we selected 30 practices for participation and randomized each to a sequence of interventions (15 for Aqueous-PREP and 20 for PREPARE). The majority of orthopedic practices included in the Aqueous-PREP and PREPARE trials were situated in level I trauma centers (100% and 87%, respectively). Orthopedic practices in the Aqueous-PREP trial operatively treated a median of 149 open fracture patients per year, included a median of 11 orthopedic surgeons, and had access to a median of 5 infection preventionists. Orthopedic practices in the PREPARE trial treated a median of 142 open fracture and 1090 closed fracture patients per year, included a median of 7.5 orthopedic surgeons, and had access to a median of 6 infection preventionists. CONCLUSIONS: The PREP-IT trials provide an example of how to follow the reporting standards for cluster randomized crossover trials by providing a clear definition of the cluster unit, a thorough description of the cluster identification and selection process, and sufficient description of key cluster characteristics. TRIAL REGISTRATION: Both trials are registered at ClinicalTrials.gov (A-PREP: NCT03385304 December 28, 2017, and PREPARE: NCT03523962 May 14, 2018).

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity is higher after caesarean section than for vaginal birth. With increasing rates of caesarean section, it is important to minimise risks to the mother as much as possible. This review focused on different skin preparations to prevent infection. This is an update of a review last published in 2018. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation (agents, methods or forms). We included studies presented only as abstracts, if there was enough information to assess risk of bias. Comparisons of interest in this review were between: different antiseptic agents (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different packages of skin preparation including a mix of agents and methods, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents. We mainly focused on the comparison between different agents, with and without the use of drapes. Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, extracted the data and checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 13 individually-randomised controlled trials (RCTs), with a total of 6938 women who were undergoing caesarean section. Twelve trials (6916 women) contributed data to this review. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in India, Egypt, Nigeria, South Africa, France, Denmark, and Indonesia. The included studies were broadly at low risk of bias for most domains, although high risk of detection bias raised some specific concerns in a number of studies. Length of stay was only reported in one comparison. Antiseptic agents Parachlorometaxylenol with iodine versus iodine alone We are uncertain whether parachlorometaxylenol with iodine made any difference to the incidence of surgical site infection (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the certainty of the evidence was very low. Adverse events (maternal or neonatal) were not reported. Chlorhexidine gluconate versus povidone iodine Moderate-certainty evidence suggested that chlorhexidine gluconate, when compared with povidone iodine, probably slightly reduces the incidence of surgical site infection (RR 0.72, 95% CI 0.58 to 0.91; 8 trials, 4323 women). This effect was still present in a sensitivity analysis after removing four trials at high risk of bias for outcome assessment (RR 0.87, 95% CI 0.62 to 1.23; 4 trials, 2037 women). Low-certainty evidence indicated that chlorhexidine gluconate, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 0.95, 95% CI 0.49 to 1.86; 3 trials, 2484 women). It is uncertain whether chlorhexidine gluconate reduces maternal skin irritation or allergic skin reaction (RR 0.64, 95% CI 0.28 to 1.46; 3 trials, 1926 women; very low certainty evidence). One small study (60 women) reported reduced bacterial growth at 18 hours after caesarean section for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70). Methods Drape versus no drape This comparison investigated the use of drape versus no drape, following preparation of the skin with antiseptics. Low-certainty evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (RR 1.29, 95% confidence interval (CI) 0.97 to 1.71; 3 trials, 1373 women), and probably makes little or no difference to the length of stay in the hospital (mean difference (MD) 0.10 days, 95% CI -0.27 to 0.46; 1 trial, 603 women; moderate-certainty evidence). One trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low certainty evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of metritis when compared with a five-minute scrub, because the certainty of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women). The studies did not report on adverse events (maternal or neonatal). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that preparing the skin with chlorhexidine gluconate before caesarean section is probably slightly more effective at reducing the incidence of surgical site infection in comparison to povidone iodine. For other outcomes examined there was insufficient evidence available from the included RCTs. Most of the evidence in this review was deemed to be very low or low certainty. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby. Well-designed RCTs, with larger sample sizes are needed. High-priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found two studies that are ongoing; we will incorporate the results of these studies in future updates of this review.

Effectiveness of Iodophor vs Chlorhexidine Solutions for Surgical Site Infections and Unplanned Reoperations for Patients Who Underwent Fracture Repair: The PREP-IT Master Protocol.

Importance: The risk of developing a surgical site infection after extremity fracture repair is nearly 5 times greater than in most elective orthopedic surgical procedures. For all surgical procedures, it is standard practice to prepare the operative site with an antiseptic solution; however, there is limited evidence to guide the choice of solution used for orthopedic fracture repair. Objective: To compare the effectiveness of iodophor vs chlorhexidine solutions to reduce surgical site infections and unplanned fracture-related reoperations for patients who underwent fracture repair. Design, Setting, and Participants: The PREP-IT (Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma) master protocol will be followed to conduct 2 multicenter pragmatic cluster randomized crossover trials, Aqueous-PREP (Pragmatic Randomized Trial Evaluating Pre-Operative Aqueous Antiseptic Skin Solution in Open Fractures) and PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities). The Aqueous-PREP trial will compare 4% aqueous chlorhexidine vs 10% povidone-iodine for patients with open extremity fractures. The PREPARE trial will compare 2% chlorhexidine in 70% isopropyl alcohol vs 0.7% iodine povacrylex in 74% isopropyl alcohol for patients with open extremity fractures and patients with closed lower extremity or pelvic fractures. Both trials will share key aspects of study design and trial infrastructure. The studies will follow a pragmatic cluster randomized crossover design with alternating treatment periods of approximately 2 months. The primary outcome will be surgical site infection and the secondary outcome will be unplanned fracture-related reoperations within 12 months. The Aqueous-PREP trial will enroll a minimum of 1540 patients with open extremity fractures from at least 12 hospitals; PREPARE will enroll a minimum of 1540 patients with open extremity fractures and 6280 patients with closed lower extremity and pelvic fractures from at least 18 hospitals. The primary analyses will adhere to the intention-to-treat principle and account for potential between-cluster and between-period variability. The patient-centered design, implementation, and dissemination of results are guided by a multidisciplinary team that includes 3 patients and other relevant stakeholders. Discussion: The PREP-IT master protocol increases efficiency through shared trial infrastructure and study design components. Because prophylactic skin antisepsis is used prior to all surgical procedures and the application, cost, and availability of all study solutions are similar, the results of the PREP-IT trials are poised to inform clinical guidelines and bring about an immediate change in clinical practice. Trial Registration: ClinicalTrials.gov Identifiers: NCT03385304 and NCT03523962.

Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo.

Biofilms are prevalent in non-healing chronic wounds and implicated in delayed healing. Tolerance to antimicrobial treatments and the host's immune system leave clinicians with limited interventions against biofilm populations. It is therefore essential that effective treatments be rigorously tested and demonstrate an impact on biofilm across multiple experimental models to guide clinical investigations and protocols. Cadexomer iodine has previously been shown to be effective against biofilm in various in vitro models, against methicillin-resistant Staphylococcus aureus biofilm in mouse wounds, and clinically in diabetic foot ulcers complicated by biofilm. Similarities between porcine and human skin make the pig a favoured model for cutaneous wound studies. Two antiseptic dressings and a gauze control were assessed against mature biofilm grown on ex vivo pig skin and in a pig wound model. Significant reductions in biofilm were observed following treatment with cadexomer iodine across both biofilm models. In contrast, silver carboxymethylcellulose dressings had minimal impact on biofilm in the models, with similar results to the control in the ex vivo model. Microscopy and histopathology indicate that the depth of organisms in wound tissue may impact treatment effectiveness. Further work on the promising biofilm efficacy of cadexomer iodine is needed to determine optimal treatment durations against biofilm.

Efficacy of Cadexomer Iodine in the Treatment of Chronic Ulcers: A Randomized, Multicenter, Controlled Trial.

INTRODUCTION: Due to being hard to heal, chronic ulcers account for high morbidity. OBJECTIVE: This study compares the safety and efficacy of 2 formulations of cadexomer iodine and standard care for the treatment of chronic ulcers. MATERIALS AND METHODS: This prospective, randomized, open-label clinical trial was conducted at 8 cities across 15 institutions in India from March 2016 to March 2017. After screening a total of 145 patients with chronic, recalcitrant ulcers, 124 were randomized to 1 of 3 treatments: 0.9% cadexomer iodine ointment plus standard care (n = 41), 0.9% cadexomer iodine powder plus standard care (n = 43), and standard care alone (n = 40). All patients completed the maximum treatment period of 12 weeks, with the exception of 8 who discontinued during the study period. At the end of the treatment period, endpoints were assessed. RESULTS: The percentage of reduction in ulcer size from baseline to the primary endpoint of 12 weeks was significantly higher with both formulations of cadexomer iodine ointment (94.3% ± 10.6%) and powder (90.4% ± 14.9%) as compared with standard care alone (67.8% ± 21.8%). The percentage of patients with complete wound healing at the end of the 12 weeks was significantly higher in patients treated with both formulations of cadexomer iodine ointment (65.8%) and powder (58.1%) as compared with standard care alone (20.0%). CONCLUSIONS: These results demonstrate that cadexomer iodine, in comparison with standard care alone, increases the percentage of reduction in ulcer size and promotes complete wound healing in chronic ulcers.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section (CS) than for vaginal birth. With the increasing rate of CS, it is important to minimise the risks to the mother as much as possible. This review focused on different forms and methods of preoperative skin preparation to prevent infection. This review is an update of a review that was first published in 2012, and updated in 2014. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (27 November 2017), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation agents, forms, and methods of application for caesarean section.Comparisons of interest in this review were between different antiseptic agents used for CS skin preparation (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different skin preparations, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents.Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, and extracted the data using a predesigned form. We checked data for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: For this update, we included 11 randomised controlled trials (RCTs), with a total of 6237 women who were undergoing CS. Ten trials (6215 women) contributed data to this review. All included studies were individual RCTs. We did not identify any quasi- or cluster-RCTs. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in Nigeria, South Africa, France, Denmark, and Indonesia.The included studies were broadly methodologically sound, but raised some specific concerns regarding risk of bias in a number of cases.Drape versus no drapeThis comparison investigated the use of a non-impregnated drape versus no drape, following preparation of the skin with antiseptics. For women undergoing CS, low-quality evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.97 to 1.71; 2 trials, 1294 women), or length of stay in the hospital (mean difference (MD) 0.10 day, 95% CI -0.27 to 0.46 1 trial, 603 women).One-minute alcohol scrub with iodophor drape versus five-minute iodophor scrub without drapeOne trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low quality evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of endomyometritis when compared with a five-minute scrub, because the quality of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women).Parachlorometaxylenol with iodine versus iodine aloneWe were uncertain whether parachlorometaxylenol with iodine before CS made any difference to the incidence of surgical site infection (RR 0.33, 95% CI 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the quality of the evidence was very low.Chlorhexidine gluconate versus povidone iodineLow-quality evidence suggested that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of surgical site infection (RR 0.80, 95% CI 0.62 to 1.02; 6 trials, 3607 women). However, surgical site infection appeared to be slightly reduced for women for whom chlorhexidine gluconate was used compared with povidone iodine after we removed four trials at high risk of bias for outcome assessment, in a sensitivity analysis (RR 0.59, 95% CI 0.37 to 0.95; 2 trials, 1321 women).Low-quality evidence indicated that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 1.01, 95% CI 0.51 to 2.01; 2 trials, 2079 women), or to reducing maternal skin irritation or allergic skin reaction (RR 0.60, 95% CI 0.22 to 1.63; 2 trials, 1521 women).One small study (60 women) reported reduced bacterial growth at 18 hours after CS for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70).None of the included trials reported on maternal mortality or repeat surgery.Chlorhexidine 0.5% versus 70% alcohol plus drapeOne trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events, and found cord blood iodine concentration to be higher in the iodine group. AUTHORS' CONCLUSIONS: There was insufficient evidence available from the included RCTs to fully evaluate different agents and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby.Most of the evidence in this review was deemed to be very low or low quality. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research.This field needs high quality, well designed RCTs, with larger sample sizes. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found four studies that were ongoing; we will incorporate the results of these studies in future updates of this review.

Effect of cadexomer iodine on the microbial load and diversity of chronic non-healing diabetic foot ulcers complicated by biofilm in vivo.

Objectives: The performance of cadexomer iodine was determined against microbial populations from chronic non-healing diabetic foot ulcers (DFUs) complicated by biofilm in vivo , using molecular, microscopy and zymography methods. Methods: Chronic non-healing DFUs due to suspected biofilm involvement were eligible for enrolment. DNA sequencing and real-time quantitative PCR was used to determine the microbial load and diversity of tissue punch biopsies obtained pre- and post-treatment. Scanning electron microscopy and/or fluorescence in situ hybridization confirmed the presence or absence of biofilm. Zymography was used to determine levels of wound proteases. Results: Seventeen participants were recruited over a 6 month period. Scanning electron microscopy and or fluorescence in situ hybridization confirmed the presence of biofilm in all samples. Eleven participants exhibited log 10 reductions in microbial load after treatment (range 1-2 log 10 ) in comparison with six patients who experienced <1 log 10 reduction ( P = 0.04). Samples were tested for levels of wound proteases pre- and post-treatment. Reductions in the microbial load correlated to reductions in wound proteases pre- and post-treatment ( P = 0.03). Conclusions: To the best of our knowledge, this study represents the first in vivo evidence, employing a range of molecular and microscopy techniques, of the ability of cadexomer iodine to reduce the microbial load of chronic non-healing DFUs complicated by biofilm. Further analyses correlating log reductions to optimal duration of therapy and improvements in clinical parameters of wound healing in a larger cohort are required.

Hyperosmotic Agents and Antibiotics Affect Dissolved Oxygen and pH Concentration Gradients in Staphylococcus aureus Biofilms.

Biofilms on wound surfaces are treated topically with hyperosmotic agents, such as medical-grade honey and cadexomer iodine; in some cases, these treatments are combined with antibiotics. Tissue repair requires oxygen, and a low pH is conducive to oxygen release from red blood cells and epithelialization. We investigated the variation of dissolved oxygen concentration and pH with biofilm depth and the variation in oxygen consumption rates when biofilms are challenged with medical-grade honey or cadexomer iodine combined with vancomycin or ciprofloxacin. Dissolved oxygen and pH depth profiles in Staphylococcus aureus biofilms were measured using microelectrodes. The presence of cadexomer iodine with vancomycin or ciprofloxacin on the surface of the biofilm permitted a measurable concentration of oxygen at greater biofilm depths (101.6 ± 27.3 µm, P = 0.02; and 155.5 ± 27.9 µm, P = 0.016, respectively) than in untreated controls (30.1 µm). Decreases in pH of ∼0.6 and ∼0.4 units were observed in biofilms challenged with medical-grade honey alone and combined with ciprofloxacin, respectively (P < 0.001 and 0.01, respectively); the number of bacteria recovered from biofilms was significantly reduced (1.26 log) by treatment with cadexomer iodine and ciprofloxacin (P = 0.002) compared to the untreated control. Combining cadexomer iodine and ciprofloxacin improved dissolved oxygen concentration and penetration depth into the biofilm, while medical-grade honey was associated with a lower pH; not all treatments established a bactericidal effect in the time frame used in the experiments.IMPORTANCE Reports about using hyperosmotic agents and antibiotics against wound biofilms focus mostly on killing bacteria, but the results of these treatments should additionally be considered in the context of how they affect physiologically important parameters, such as oxygen concentration and pH. We confirmed that the combination of a hyperosmotic agent and an antibiotic results in greater dissolved oxygen and reduced pH within an S. aureus biofilm.