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.

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.

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.

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.

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.

The expanding horizon of prosthetic joint infections.

Prosthetic joint infection (PJI) is a serious and potentially devastating complication of arthroplasty. Prior arthroplasty, immunosuppression, severe comorbid conditions, and prolonged surgical duration are important risk factors for PJI. More than half of the cases of PJI are caused by Staphylococcus aureus and coagulase-negative staphylococci. The biofilm plays a central role in its pathogenesis. The diagnosis of PJI requires the presence of purulence, sinus tract, evidence of inflammation on histopathology, or positive microbiologic cultures. The use of diagnostic imaging techniques is generally limited but may be helpful in selected cases. The most effective way to prevent PJI is to optimize the health of patients, using antibiotic prophylaxis in a proper and timely fashion. Management of PJI frequently requires removal of all hardware and administration of intravenous antibiotics. This review summarizes and analyzes the results of previous reports of PJI and assesses the prevention and management of this important entity.

Short versus long course of antibiotics for catheter-associated urinary tract infections in patients with spinal cord injury: a randomized controlled noninferiority trial.

OBJECTIVE: To assess the applicability of a short-course regimen of antibiotics for managing catheter-associated urinary tract infection (CA-UTI) in patients with spinal cord injury (SCI). DESIGN: Randomized, controlled, noninferiority trial. SETTING: Medical center. PARTICIPANTS: Patients with SCI who had CA-UTI (N=61). INTERVENTIONS: Patients were randomized to receive either a 5-day regimen of antibiotics after catheter exchange (experimental group) or a 10-day regimen of antibiotics with catheter retention (control group). Noninferiority was prespecified with a margin of 10%. MAIN OUTCOME MEASURE: Clinical cure at the end of therapy. RESULTS: Of the 61 patients enrolled in this study, 6 patients were excluded because of bacteremia or absence of urinary symptoms. All patients (100%) achieved clinical cure at the end of therapy. The rates of microbiologic response were 82.1% in the experimental group and 88.9% in the control group (upper boundary 95% confidence interval (CI) for difference, 26%). The rates of resolution of pyuria were 89.3% in the experimental group and 88.9% in the control group (upper boundary 95% CI for difference, 16%). Patients in the experimental group had higher rates of CA-UTI recurrence than the control group. The rates of new CA-UTI, diarrhea, and Clostridium difficile colitis were similar in the 2 treatment arms. CONCLUSIONS: The primary endpoint of the study was met, indicating that the 5-day regimen with catheter exchange was noninferior to the 10-day regimen with catheter retention on the basis of clinical cure. Criteria for noninferiority on the basis of microbiologic response and resolution of pyuria were not met.

North American consensus document on infection of penile prostheses.

OBJECTIVE: To issue a consensus document on the prevention, management, and research of infection associated with penile prostheses, as neither professional associations nor governmental entities have issued guidelines that are specific to this infection. METHODS: Sixteen North American experts on infection of penile prostheses were identified and assembled to select and discuss certain issues related to infection of penile prostheses. After performing an extensive search of clinically important issues in published reports, the 16 experts met twice in person to finalize the selection, discuss the issues that were deemed most important, and issue pertinent recommendations. RESULTS: Although many subjects relevant to infection of penile prostheses were initially identified, the experts selected 10 issues as currently being the most important issues and for which there exists some support in the published data. The examined issues involved prevention, management, or research of infections associated with penile prostheses. CONCLUSION: In the absence of pertinent guidelines, the consensus document issued by experts in the field of prosthetic urology is anticipated to improve the quality of patient care, streamline the prevention and management of infected penile prostheses, and stimulate collaborative research. Although this consensus document could serve as best practice recommendations, the lack of adherence to these recommendations would not indicate improper care.

Clinical significance of Staphylococcus aureus bacteriuria at a tertiary care hospital.

OBJECTIVES: Staphylococcus aureus bacteriuria has been associated with invasive S. aureus disease. The current project describes the clinical significance of S. aureus bacteriuria. METHODS: We conducted a retrospective chart review of patients who had S. aureus bacteriuria at the Michael E. DeBakey Veterans Affairs Medical Center, 2008-2010. RESULTS: A total of 326 patients were included. Invasive S. aureus disease was documented within 12 months of bacteriuria in 56 patients (22.3% of methicillin-resistant S. aureus (MRSA) cases and 8.4% of methicillin-sensitive S. aureus (MSSA), p = 0.002). Multiple logistic regression indicated that MRSA bacteriuria (odds ratio (OR) 2.91, p = 0.010), absence of symptoms suggestive of a urinary tract infection (UTI) (OR 3.21, p = 0.019), inpatient status (OR 4.72, p = 0.003), and receipt of antibiotics active against S. aureus (OR 6.41, p < 0.001) were significantly associated with the presence of invasive S. aureus disease. Seventy-seven patients (23.6%) died within 12 months of the documented S. aureus bacteriuria. Age (OR 1.02, p = 0.025), absence of pyuria (OR 2.00, p = 0.029), the presence of invasive S. aureus disease (OR 2.05, p = 0.033), and inpatient status (OR 3.62, p < 0.001) were significantly associated with death. CONCLUSIONS: S. aureus bacteriuria is associated with significant morbidity and mortality. Patients without UTI symptoms, those with MRSA bacteriuria, and those without pyuria were more to likely to have worse outcomes (invasive S. aureus disease or death). Obtaining blood cultures should be considered in these cases.

Bioprosthetic mitral valve endocarditis after percutaneous device closure of severe paravalvular leak.

A large mitral paravalvular leak in a 63-year-old patient was closed by percutaneous placement of 2 Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, MN) devices. The patient had a residual paravalvular leak and subsequently developed infective endocarditis that was successfully treated by removal of all hardware and implantation of a new valve. Transcatheter treatment of paravalvular leaks may be useful in select patients who are poor candidates for open surgery; however, one must be aware of the potential complications. This report underscores the risk of device infection that may be increased if there is turbulence related to residual paravalvular leaks.