Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy.

The BSAC guidelines on treatment of infectious endocarditis (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and prosthetic valve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring to in vitro or animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery.

Antimicrobial activity of a chlorhexidine intravascular catheter site gel dressing.

OBJECTIVES: The antimicrobial efficacy of a chlorhexidine gluconate (CHG) intravascular catheter gel dressing was evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and an extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. Chlorhexidine deposition on the skin surface and release from the gel were determined. METHODS: The antimicrobial efficacy was evaluated in in vitro studies following microbial inoculation of the dressing and application of the dressing on the inoculated surface of a silicone membrane and donor skin [with and without a catheter segment and/or 10% (v/v) serum] on diffusion cells. Antimicrobial activity was evaluated for up to 7 days. Chlorhexidine skin surface deposition and release were also determined. RESULTS: MRSA and E. coli were not detectable within 5 min following direct inoculation onto the CHG gel dressing. On the silicone membrane, 3 log and 6 log inocula of MRSA were eradicated within 5 min and 1 h, respectively. Time to kill was prolonged in the presence of serum and a catheter segment. Following inoculation of donor skin with 6 log cfu of MRSA, none was detected after 24 h. Chlorhexidine was released from the gel after a lag time of 30 min and increasing amounts were detected on the donor skin surface over the 48 h test period. The CHG gel dressing retained its antimicrobial activity on the artificial skin for 7 days. CONCLUSIONS: The CHG intravascular catheter site gel dressing had detectable antimicrobial activity for up to 7 days, which should suppress bacterial growth on the skin at the catheter insertion site, thereby reducing the risk of infection.

Enhanced chlorhexidine skin penetration with eucalyptus oil.

BACKGROUND: Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic. METHOD: Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (µg/mg of skin) was determined to a skin depth of 1500 µm by high performance liquid chromatography (HPLC). RESULTS: The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. CONCLUSION: The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis.

Prevention of central venous catheter-related infection: update.

Central venous catheters (CVCs) are an essential part of modern-day healthcare, but infections associated with these devices continue to cause significant morbidity and mortality. There are many approaches for the prevention of CVC-related infection and these are outlined in national guidelines. The Department of Health Saving Lives campaign has developed a care-bundle for the prevention of CVC-related infections that focuses on the fundamental actions to be undertaken during the catheter insertion process and ongoing care. If the rate of catheter-related infection remains high despite the implementation of these infection prevention strategies, the use of novel antimicrobial technologies and practices may be considered. These include CVCs that contain antimicrobial agents, such as antiseptics or antibiotics, needleless intravenous (IV) access devices coated with silver and/or chlorhexidine, IV dressings incorporating chlorhexidine, and the use of antimicrobial catheter lock solutions, such as antibiotics, chelators or ethanol. This article outlines the different types of CVCs available, the risk of infection associated with their use and established and novel measures for prevention of these infections.

Progress in the prevention of surgical site infection.

PURPOSE OF REVIEW: The present review summarizes some of the key papers on the prevention of surgical site infections (SSI) published in 2008. RECENT FINDINGS: The National Institute for Health and Clinical Excellence published guidelines on the prevention and management of SSI. These guidelines follow a similar format to those published previously. There are, however, some important differences to previous recommendations and these are outlined in this current article. Other publications have provided additional evidence that suggests certain antiseptic agents are more efficacious than others for surgical hand antisepsis. Staphylococcus aureus decolonization has also been studied and noted to be of benefit for the prevention of SSI. Other research studies have focused on patient homeostasis, including the use of supplemental perioperative oxygen, which has resulted in mixed findings. Finally, the use of surveillance to evaluate the efficacy of 'care bundles' has been reported, which brings together many different approaches for the prevention of SSI. SUMMARY: Several evaluations of pre, peri and postoperative strategies for the prevention of SSI have been published in 2008, some of which have raised some fundamental questions.

A clinical evaluation of two central venous catheter stabilization systems.

BACKGROUND: Central venous catheters (CVCs) are commonly secured with sutures which are associated with microbial colonization and infection. We report a comparison of a suture-free system with standard sutures for securing short-term CVC in an international multicentre, prospective, randomized, non-blinded, observational feasibility study. Consented critical care patients who had a CVC inserted as part of their clinical management were randomized to receive either sutures or the suture-free system to secure their CVC. The main outcome measures were CVC migration (daily measurement of catheter movement) and unplanned catheter removals. RESULTS: The per cent of unplanned CVC removal in the two study groups was 2% (suture group 2 out of 86 patients) and 6% (suture-free group 5 out of 85 patients). Both securement methods were well tolerated in terms of skin irritation. The time and ease of application and removal of either securement systems were not rated significantly different. There was also no significant difference in CVC migration between the two securement systems in exploratory univariate and multivariate analyses. Overall, 42% (36 out of 86) of the CVC secured with sutures and 56% (48 out of 85) of the CVC secured with the suture-free securement system had CVC migration of ≥ 2 mm. CONCLUSIONS: The two securement systems performed similarly in terms of CVC migration and unplanned removal of CVC; however, the feasibility study was not powered to detect statistically significant differences in these two parameters. TRIAL REGISTRATION: ISRCTN, ISRCTN13939744. Registered 9 July 2015, http://www.isrctn.com/ISRCTN13939744 .

Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. METHOD: The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. RESULTS: Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%]; P=.01) or in patients with NVE due to viridans group streptococci (149 [44%]; P=.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively; P=.44); the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%]; P=.01). Persistent bacteremia (odds ratio, 2.65; 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35; 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86; 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). CONCLUSIONS: CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.

Antimicrobial central venous catheters in adults: a systematic review and meta-analysis.

Several antimicrobial central venous catheters (CVCs) are available. We did a meta-analysis to assess their efficacy in reducing microbial colonisation and preventing catheter-related bloodstream infection (CRBSI). An extensive literature search of articles in any language was undertaken. We assessed randomised clinical trials in which available antimicrobial CVCs were compared with either a standard CVC or another antimicrobial CVC. Outcomes assessed were microbial colonisation of CVCs and CRBSI. The first-generation chlorhexidine-silver sulfadiazine (CSS) CVCs reduce colonisation (odds ratio [OR] 0.51 [95% CI 0.42-0.61]) and CRBSI (OR 0.68 [0.47-0.98]), as do the minocycline-rifampicin CVCs (OR 0.39 [0.27-0.55] and OR 0.29 [0.16-0.52], respectively). The minocycline-rifampicin CVCs outperformed the first-generation CSS CVCs in reducing colonisation (OR 0.34 [0.23-0.49]) and CRBSI (OR 0.18 [0.07-0.51]). Many shortcomings in methodological quality limit our interpretation of the study results. However, the available evidence suggests that use of CSS and minocycline-rifampicin CVCs are useful if the incidence of CRBSI is above institutional goals despite full implementation of infection prevention interventions.

An in vitro comparison of standard cleaning to a continuous passive disinfection cap for the decontamination of needle-free connectors.

Background: The optimal decontamination method for needle-free connectors is still unresolved. The objective of this study was to determine if a continuous passive disinfection cap is as effective as standard cleaning for the microbial decontamination of injection ports of two types of needle-free connectors. Methods: The injection ports of needle-free connectors were inoculated with Staphylococcus aureus and allowed to dry. Disinfection caps containing 70% (v/v) isopropyl alcohol (IPA) were attached to the connectors for one, three or 7 days and were compared with needle-free connectors cleaned with 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) IPA. The number of S. aureus remaining on the injection ports was evaluated. Median log10 reductions and 95% confidence interval (CI) were calculated and data analyzed using the Mann-Whitney test. Results: The application of the disinfection cap resulted in a significantly higher reduction in S. aureus than the 2% (w/v) CHG in 70% (v/v) IPA wipe, achieving a > 5 Log10 reduction in CFU at each time point. Conclusions: The disinfection caps resulted in a significantly higher reduction in S.aureus on the injection ports when compared to the use of a 2% (w/v) CHG in 70% (v/v) IPA wipe. This offers an explanation for the lower rates of central-line associated bloodstream infection (CLABSI) associated with the use of disinfection caps reported in clinical studies.

Evaluation of routine microbiological techniques for establishing the diagnosis of catheter-related bloodstream infection caused by coagulase-negative staphylococci.

Microbiological diagnosis of catheter-related bloodstream infection (CR-BSI) is often based on isolation of indistinguishable micro-organisms from an explanted catheter tip and blood culture, confirmed by antibiograms. Whether phenotypic identification of coagulase-negative staphylococci (CoNS) allows an accurate diagnosis of CR-BSI to be established was evaluated. Eight patients with a diagnosis of CR-BSI had CoNS isolated from pure blood cultures and explanted catheter tips which were considered as indistinguishable strains by routine microbiological methods. For each patient, an additional three colonies of CoNS isolated from the blood and five from the catheter tip were subcultured and further characterized by antibiogram profiles, analytical profile index (API) biotyping and PFGE. PFGE distinguished more strains of CoNS compared to API biotyping or antibiograms (17, 10 and 11, respectively). By PFGE, indistinguishable micro-organisms were only isolated from pure blood and catheter tip cultures in four out of eight (50%) patients thus supporting the diagnosis of CR-BSI. In another patient, indistinguishable micro-organisms were identified in both cultures; however, other strains of CoNS were also present. The remaining three patients had multiple strains of CoNS, none of which were indistinguishable in the tip and blood cultures, thus questioning the diagnosis of CR-BSI. Phenotypic characterization of CoNS lacked discriminatory power. Current routine methods of characterizing a limited number of pooled colonies may generate misleading results as multiple strains may be present in the cultures. Multiple colonies should be studied using a rapid genotypic characterization method to confirm or refute the diagnosis of CR-BSI.

Infection risks associated with needleless intravenous access devices.

Needleless intravenous (i.v.) access devices were initially introduced into clinical practice to reduce the rate of i.v. catheter-related needlestick injuries. Their efficacy for this purpose has been confirmed in subsequent reports. However, since their introduction approximately 15 years ago there have been conflicting reports about the risk of i.v. catheter-related bloodstream infection. This article reviews the risk of catheter-related bloodstream infection associated with needleless i.v. access devices and outlines the types of needleless i.v. access devices available.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates.

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin-resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease.

Molecular analysis of methicillin-resistant Staphylococcus aureus reveals an absence of plasmid DNA in multidrug-resistant isolates.

The number, diversity and restriction enzyme fragmentation patterns of plasmids harboured by 44 multidrug-resistant hospital-acquired methicillin-resistant Staphylococcus aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK) were compared. In addition, pulsed-field gel electrophoresis (PFGE) type following SmaI chromosomal digest and SCCmec element type assignment were ascertained for each isolate. All MR-HA-MRSA and MR-CA-MRSA isolates possessed the type II SCCmec, harboured no plasmid DNA and belonged to one of five PFGE types. Forty-three out of 50 HA-MRSA isolates and all 34 CA-MRSA isolates possessed the type IV SCCmec and all but 10 of the type IV HA-MRSA isolates and nine CA-MRSA isolates carried one or two plasmids. The 19 non-multidrug-resistant isolates (NMR) that did not harbour plasmids were only resistant to methicillin whereas all the NMR isolates harbouring at least one plasmid were resistant to at least one additional antibiotic. We conclude that although plasmid carriage plays an important role in antibiotic resistance, especially in NMR-HA-MRSA and CA-MRSA, the multidrug resistance phenotype from HA-MRSA is not associated with increased plasmid carriage and indeed is characterised by an absence of plasmid DNA.

Staphylococcus aureus endocarditis: a consequence of medical progress.

CONTEXT: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. OBJECTIVES: To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). CONCLUSIONS: S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.

Analysis of clinical isolates of Propionibacterium acnes by optimised RAPD.

Random amplification of polymorphic DNA (RAPD) was evaluated as a genotypic method for typing clinical strains of Propionibacterium acnes. RAPD can suffer from problems of reproducibility if parameters are not standardised. In this study the reaction conditions were optimised by adjusting template DNA concentration and buffer constituents. All isolates were typeable using the optimised RAPD protocol which was found to be highly discriminatory (Simpson's diversity index, 0.98) and reproducible. Typing of P. acnes by optimised RAPD is an invaluable tool for the epidemiological investigation of P. acnes for which no other widely accepted method currently exists.

Impact of catheter antimicrobial coating on species-specific risk of catheter colonization: a meta-analysis.

BACKGROUND: Antimicrobial catheters have been utilized to reduce risk of catheter colonization and infection. We aimed to determine if there is a greater than expected risk of microorganism-specific colonization associated with the use of antimicrobial central venous catheters (CVCs). METHODS: We performed a meta-analysis of 21 randomized, controlled trials comparing the incidence of specific bacterial and fungal species colonizing antimicrobial CVCs and standard CVCs in hospitalized patients. RESULTS: The proportion of all colonized minocycline-rifampin CVCs found to harbor Candida species was greater than the proportion of all colonized standard CVCs found to have Candida. In comparison, the proportion of colonized chlorhexidine-silver sulfadiazine CVCs specifically colonized with Acinetobacter species or diphtheroids was less than the proportion of similarly colonized standard CVCs. No such differences were found with CVCs colonized with staphylococci. CONCLUSION: Commercially-available antimicrobial CVCs in clinical use may become colonized with distinct microbial flora probably related to their antimicrobial spectrum of activity. Some of these antimicrobial CVCs may therefore have limited additional benefit or more obvious advantages compared to standard CVCs for specific microbial pathogens. The choice of an antimicrobial CVC may be influenced by a number of clinical factors, including a previous history of colonization or infection with Acinetobacter, diphtheroids, or Candida species.

A comparative study to evaluate surface microbial contamination associated with copper-containing and stainless steel pens used by nurses in the critical care unit.

A clinical study was undertaken to compare the surface microbial contamination associated with pens constructed of either a copper alloy or stainless steel used by nurses on intensive care units. A significantly lower level of microbial contamination was found on the copper alloy pens.

Diagnosis of central venous catheter related infection in adult patients.

Intravascular catheters are one of the main causes of bacteraemia and septicaemia in hospitalised patients and continue to be associated with a significant morbidity and mortality. Two main types of infections occur, they can be either localised at the catheter insertion site of systemic with a septicaemia. The clinical parameters related to these infections are presented. The laboratory diagnosis of these infections is also extensively reviewed and recommendations are made as to the most appropriate diagnostic method to be used.