Does antimicrobial coating and impregnation of urinary catheters prevent catheter-associated urinary tract infection? A review of clinical and preclinical studies.

Introduction: Catheter-associated urinary tract infection (CAUTI) is one of the most common nosocomial infections in hospitals, accounting for 36% of all health care-associated infections. Areas covered: We aimed to address the potential impact of antimicrobial coating of catheter materials for the prevention of CAUTI and to analyze the progress made in this field. We conducted literature searches in the PubMed, Embase, and Cochrane Library databases, and found 578 articles. Data from 60 articles in either the preclinical or clinical stage were analyzed in this expert review. Expert opinion: The literature review revealed many promising methods for preventing CAUTI. Recent studies have suggested the combination of silver-based products and antibiotics, owing to their synergistic effect, to help address the problem of antibiotic resistance. Other coating materials that have been tested include nitric oxide, chlorhexidine, antimicrobial peptides, enzymes, and bacteriophages. Because of heterogeneity among studies, it is difficult to reliably comment on the clinical efficacy of different coating materials. Future research should focus on double-blind randomized clinical trials for evaluating the role of these potential coating agents.

A Trans-Atlantic Perspective on Stagnation in Clinical Translation of Antimicrobial Strategies for the Control of Biomaterial-Implant-Associated Infection.

Current regulatory requirements impede clinical translation and market introduction of many new antimicrobial combination implants and devices, causing unnecessary patient suffering, doctor frustration, and costs to healthcare payers. Regulatory requirements of antimicrobial combination implants and devices should be thoroughly revisited and their approval allowed based on enrichment of benefit demonstrations from high-risk patient groups and populations or device components to facilitate their clinical translation. Biomaterial implant and devices equipped with antimicrobial strategies and approved based on enrichment claims should be mandatorily enrolled in global registry studies supervised by regulatory agencies for a minimum five-year period or until statistically validated evidence for noninferiority or superiority of claims is demonstrated. With these recommendations, this trans-Atlantic consortium of academicians and clinicians takes its responsibility to actively seek to relieve the factors that stagnate downward clinical translation and availability of antimicrobial combination implants and devices. Improved dialogue between the various key players involved in the current translational blockade, which include patients, academicians and doctors, policymakers, regulatory agencies, manufacturers, and healthcare payers, is urgently needed.

Private Rooms in Low Acuity Settings: A Systematic Review of the Literature.

OBJECTIVES: Determine if the peer-reviewed evidence supports single-patient ward bedrooms in low-acuity care settings within a hospital. BACKGROUND: New evidence exists since the 2006 Facility Guideline Institute guideline recommended single-bedded rooms (SBRs) in low-acuity care settings. Additionally, prior studies evaluated high-acuity care settings (e.g., critical care) in their recommendations on SBRs. There is a need to reevaluate the evidence. METHODS: A systematic review of the literature was completed including electronic and hand searches of references. A data extraction form was utilized. Two reviewers evaluated the studies independently. Studies that were included examined the effect of single-patient rooms on medical surgical ward beds only. Each study was graded using accepted clinical evidence grading instruments. RESULTS: Over 1,400 records were identified. After excluding studies, a total of 49 records were graded. The highest quality evidence identified (Center for Evidence-Based Medicine [CEBM]: 2a, 2b, and Grading of Recommendations, Assessment, Development, and Evaluation [GRADE] C) did not support the use of single-patient rooms for reducing infections, for minimizing patient falls, for reducing medication errors, or for patient satisfaction. Operational efficiencies were improved with SBRs but only addressed the maternity ward. The lowest quality evidence (CEBM: 4/5 and GRADE D) supported the use of single-patient rooms. CONCLUSIONS: Based on CEBM and GRADE assessments, there is a lack of high-quality data supporting the use of low-acuity SBRs throughout the entire hospital. Furthermore, it is recommended that more research be conducted on the effect of SBRs, so higher quality evidence is developed.

Coating of silicone with mannoside-PAMAM dendrimers to enhance formation of non-pathogenic Escherichia coli biofilms against colonization of uropathogens.

Bacterial interference using non-pathogenic Escherichia coli 83972 is a novel strategy for preventing catheter-associated urinary tract infection (CAUTI). Crucial to the success of this strategy is to establish a high coverage and stable biofilm of the non-pathogenic bacteria on the catheter surface. However, this non-pathogenic strain is sluggish to form biofilms on silicone as the most widely used material for urinary catheters. We have addressed this issue by modifying the silicone catheter surfaces with mannosides that promote the biofilm formation, but the stability of the non-pathogenic biofilms challenged by uropathogens over long-term remains a concern. Herein, we report our study on the stability of the non-pathogenic biofilms grown on propynylphenyl mannoside-modified silicone. The result shows that 94% non-pathogenic bacteria were retained on the modified silicone under >0.5 Pa shear stress. After being challenged by three multidrug-resistant uropathogenic isolates in artificial urine for 11 days, large amounts (>4 × 106 CFU cm-2) of the non-pathogenic bacteria remained on the surfaces. These non-pathogenic biofilms reduced the colonization of the uropathogens by >3.2-log. STATEMENT OF SIGNIFICANCE: In bacterial interference, the non-pathogenic Escherichia coli strains are sluggish to form biofilms on the catheter surfaces, due to rapid removal by urine flow. We have demonstrated a solution to this bottleneck by pre-functionalization of mannosides on the silicone surfaces to promote E. coli biofilm formation. A pre-conjugated high affinity propynylphenyl mannoside ligand tethered to the nanometric amino-terminated poly(amido amine) (PAMAM) dendrimer is used for binding to a major E. coli adhesin FimH. It greatly improves the efficiency for the catheter modification, the non-pathogenic biofilm coverage, as well as the (long-term) stability for prevention of uropathogen infections.

An update on emerging therapies for urinary tract infections.

INTRODUCTION: Urinary tract infections (UTIs) are the most common healthcare-acquired infections, and are associated with high morbidity and mortality. Worldwide use of antibiotics has led to a significant rise in resistant uropathogens emanating from both hospitals and communities. The huge concern of multidrug resistance (MDR) has led the Food and Drug Administration (FDA) to encourage drug companies to invest in the development of new antibiotics. Area covered: In this review we summarized data on already approved antibiotics, and selected emerging therapies that are currently in phase II and III trials with emphasis on complicated urinary tract infections (cUTIs). We performed our search using PubMed, ClinicalTrials.gov, Google Scholar and Pharmaprojects. Expert opinion: Efficacious antimicrobials are needed to overcome MDR organisms. There are several dugs in initial and later stages of development, but most of them lack full spectrum of activity against some Gram-negative organisms, particularly against MDR Pseudomonas aeruginosa. Better understanding of the pathogenesis of UTI and genetic engineering of pathogens can provide new drugs to combat resistance in the future.

Association of Airborne Microorganisms in the Operating Room With Implant Infections: A Randomized Controlled Trial.

OBJECTIVE To evaluate the association of airborne colony-forming units (CFU) at incision sites during implantation of prostheses with the incidence of either incisional or prosthesis-related surgical site infections. DESIGN Randomized, controlled trial. SETTING Primary, public institution. PATIENTS Three hundred patients undergoing total hip arthroplasty, instrumented spinal procedures, or vascular bypass graft implantation. METHODS Patients were randomly assigned in a 1:1 ratio to either the intervention group or the control group. A novel device (Air Barrier System), previously shown to reduce airborne CFU at incision sites, was utilized in the intervention group. Procedures assigned to the control group were performed without the device, under routine operating room atmospheric conditions. Patients were followed up for 12 months to determine whether airborne CFU levels at the incision sites predicted the incidence of incisional or prosthesis-related infection. RESULTS Data were available for 294 patients, 148 in the intervention group and 146 in the control group. CFU density at the incision site was significantly lower in the intervention group than in the control group (P<.001). The density of airborne CFU at the incision site during the procedures was significantly related to the incidence of implant infection (P=.021). Airborne CFU densities were 4 times greater in procedures with implant infection versus no implant infection. All 4 of the observed prosthesis infections occurred in the control group. CONCLUSION Reduction of airborne CFU specifically at the incision site during operations may be an effective strategy to reduce prosthesis-related infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01610271 Infect Control Hosp Epidemiol 2016;1-8.

Antibiotics and antiseptics for preventing infection in people receiving revision total hip and knee prostheses: a systematic review of randomized controlled trials.

BACKGROUND: Infection rates in revision (second and subsequent) major joint arthroplasty continues to be a significant issue with rates 2-3 times those of primary procedures. The effect of antibiotic and antiseptic prophylaxis on outcomes for this type of surgery has not been adequately reviewed. METHODS: A systematic search of the main databases for randomized controlled trials (RCTs) evaluating antibiotics and antiseptics was conducted to evaluate the predetermined endpoints of infection. RESULTS: There were five (5) RCTs identified that examined the effects of antibiotic and antiseptic prophylaxis on infections after revision total hip arthroplasty [THA] (total of 304 participants) and total knee arthroplasty [TKA] (total of 206 participants). For TKA, preoperative systemic intravenous (IV) antibiotic prophylaxis plus antibiotic cement may be effective in reducing the incidence of infection in revision TKA at 8+ years. These results however should be interpreted with caution due to the significant biases. For revision THA, there is no RCT evidence that antibiotics/antiseptics have any effect on the infection rate. CONCLUSIONS: There is a lack of high quality data demonstrating an effect of antibiotics or antiseptics on infection rates in revision THA/TKA. Considering the rate of infections in revisions is 2-3X that of primary procedures and; there is a consensus recommendation to use similar antibiotic and antiseptic regimens in both primary and revision procedures, there is a need for high quality studies in revision THA/TKA.

A Randomized Study Evaluating Oral Fusidic Acid (CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified Drug-Drug Interaction.

BACKGROUND: Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described. METHODS: In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively. RESULTS: Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected. CONCLUSIONS: The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research. CLINICAL TRIALS REGISTRATION: NCT01756924.

Predicting clinical outcomes in patients with negative peripheral and positive central blood culture with coagulase negative Staphylococcus species.

OBJECTIVES: Clinical outcomes in patients with negative peripheral and positive central blood culture with coagulase negative staphylococci (CoNS) based on different treatment approach such as intravenous antibiotics, removal of CVC, combined approach or just observation are not known. METHODS: We conducted a retrospective review of patients with negative peripheral and paired positive central blood culture with CoNS admitted at our affiliated hospital between 2008 to 2013. We compared clinical outcomes such as bacteremia, catheter related blood stream infection (CRBSI), mortality and Intensive care unit (ICU) admission over the next 90 days between the 4 groups based on the treatment approach: (1) No treatment received, 2) catheter removed, no antibiotics administered, 3) antibiotics administered, catheter not removed and 4) antibiotics administered, catheter removed). Logistic regression was used to assess the association between treatment approach and outcomes after adjusting for confounding variables. RESULTS: 181 patients were included in the study and followed for 90 days after their initial positive blood cultures. 25 patients (14%) had bacteremia, 4 patients (2%) had CRBSI, 40 patients (22%) died and 10 patients (6%) had an ICU admission in the next 90 days. None of the outcomes differed statistically between the 4 groups. CONCLUSION: Our study is the first to report no difference in the clinical outcomes in patients with negative peripheral and positive central blood culture with CoNS when compared based on treatment approach. Our study provides initial evidence that treating patients with an isolated central blood culture with CoNS does not change short term clinical outcomes.

Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Systematic review and meta-analysis of randomized controlled trials of antibiotics and antiseptics for preventing infection in people receiving primary total hip and knee prostheses.

Infection rates in primary (first-time) major joint arthroplasty continue to be a significant issue. The effect of antibiotic and antiseptic prophylaxis on outcomes for this type of surgery has not been adequately reviewed. A systematic search of the main databases for randomized controlled trials (RCTs) evaluating antibiotics and antiseptics was conducted to evaluate the predetermined endpoints of infection, adverse events, costs, quality of life, and concentration levels of antibiotics. A meta-analysis using pooled effect estimates and fixed-effect and random-effect models of risk ratios (RR), calculated with 95% confidence intervals (CI), was utilized. Thirty (30) RCTs examined the effects of antibiotic and antiseptic prophylaxis on infections after primary total hip arthroplasty (THA) (total of 11,597 participants) and total knee arthroplasty (TKA) (total of 6,141 participants). For THA, preoperative systemic intravenous (i.v.) antibiotic prophylaxis may be effective in reducing the incidence of infection after THA from 6 months to ≥5 years. For TKA, there is no RCT evidence that antibiotics and/or antiseptics have any effect on infection rate. Preoperative systemic antibiotic prophylaxis in primary THA may be effective at reducing infection rate. There is no evidence that timing, route of administration, or concentration levels have an effect on reducing infections, adverse events, or costs in THA or TKA. Many of the trials included in this study were published in the 1980s and 1990s. Thus, it would be important to replicate a number of them based on current patient demographics and incidence of bacterial resistance.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

BACKGROUND: Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. METHODS: ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. FINDINGS: Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. INTERPRETATION: Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. FUNDING: Cubist Pharmaceuticals.

Infections Associated with Inflatable Penile Prostheses.

INTRODUCTION: The implantation of inflatable penile prosthesis (IPP) has become a successful method for the treatment of erectile dysfunction. Infections are rare but they can result in devastating complications following surgical implantation of the prosthesis. AIM: To discuss pathogenesis, risk factors, and microbiology of IPP infections, summarize clinical manifestation and diagnostic methods, and discuss future directions of prevention and management. METHODS: A PubMed search was performed of all articles published from 1960 to present relating to IPP infections. MAIN OUTCOME MEASURE AND RESULTS: Skin flora organisms such as Staphylococcus epidermis are the most common source of infection. Several host and surgical risk factors for prosthesis infection have been demonstrated, including uncontrolled diabetes mellitus and previous surgical interventions. Biofilms play an important role in the pathogenesis of device-related infections. Pain, fever, drainage, and device extrusions are suggestive of IPP infection. Preventive methods include preoperative skin cleansing, systemic antibiotic prophylaxis, and the use of surface-modified prostheses. The most frequently utilized surgical management is a single-stage approach that comprises aggressive irrigation and debridement, removal of all components of the infected prosthesis, and placement of a new IPP in the same surgical setting. CONCLUSION: Advances in systemic antimicrobial prophylaxis, skin cleansing and surface-modification of the devices, as well as a number of other potentially protective measures, have decreased the rates of infections. Currently, most infected IPP are surgically managed by adopting the salvage approach. Al Mohajer M and Darouiche RO. Infections associated with inflatable penile prostheses. Sex Med Rev 2014;2:134-140.