T.S.J. Elliott

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.

Association between sciatica and Propionibacterium acnes

We hypothesised that the inflammation seen around the nerve root in patients with sciatica may be caused by microbial infection. We used a newly developed serological test to diagnose deep-seated infections caused by low virulent gram-positive microorganisms. 43 of 140 (31%) patients with sciatica tested positive. Intervertebral disc material from a further 36 patients with severe sciatica who had undergone microdiscectomy was cultured for the presence of microorganisms. 19 of these patients (53%) had positive cultures after long-term incubation. Propionibacterium acnes was isolated from 16 of the 19 (84%) positive samples. Low virulent microorganisms, in particular P acnes, might be causing a chronic low-grade infection in the lower intervertebral discs of patients with severe sciatica. These microorganisms could have gained access to the spinal disc after previous minor trauma.

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.

Antibiotic prophylaxis in gastrointestinal endoscopy

Bacteraemia is common following some forms of gastrointestinal endoscopic therapy, such as dilatation or injection sclerotherapy, and can occur with diagnostic endoscopy alone. Fortunately complications resulting from dissemination of endogenous bacteria are uncommon, and infective endocarditis is an extremely rare complication. Furthermore, for most diagnostic and therapeutic procedures there is scant evidence that antibiotic prophylaxis can reduce the incidence of infective complications. The area that has attracted the most controversy in recent years has been the use of antibiotics to prevent infective endocarditis. The recommendations by the American Heart Association (AHA)1 have traditionally guided the advice of the national bodies representing endoscopic practice,2 3 including the British Society of Gastroenterology (BSG).4 The traditional guidance has been that patients at high risk of endocarditis, such as those with a prosthetic (ie, tissue or mechanical) valve and/or a past history of endocarditis should receive antibiotics for all endoscopic procedures. More recently the European Society of Cardiology recommended antibiotic prophylaxis to cover therapeutic endoscopy in patients with acquired valvular heart disease,5 and the British Cardiovascular Society went even further, advising antibiotic prophylaxis for patients at moderate risk of endocarditis undergoing any endoscopic procedure.6 The Endoscopy Committee of the BSG recognised the need for consensus on this issue, and convened a Working Party in the spring of 2006. The membership, comprised doctors with a special interest in gastroenterology, gastroenterologists, cardiologists and microbiologists. The gastroenterologists and microbiologists from this Working Party also took the opportunity to review the evidence underpinning the use of antibiotic prophylaxis in other areas of endoscopic practice, in particular endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous endoscopic gastrostomy (PEG). In view of new guidance from the AHA, and from the National Institute for Health and Clinical Excellence (NICE), the Working Party reconvened in 2008 to reconsider, in …

A randomized, prospective clinical trial to assess the potential infection risk associated with the PosiFlow needleless connector.

The microbial contamination rate of luers of central venous catheters (CVCs) with either PosiFlow needleless connectors or standard caps attached was investigated. The efficacy of 70% (v/v) isopropyl alcohol, 0.5% (w/v) chlorhexidine in gluconate 70% (v/v) isopropyl alcohol and 10% (w/v) aqueous povidone-iodine to disinfect the intravenous connections was also assessed. Seventy-seven patients undergoing cardiac surgery who required a CVC as part of their clinical management were randomly allocated either needleless connectors or standard caps. Patients were also designated to receive chlorhexidine/alcohol, isopropyl alcohol or povidone-iodine for pre-CVC insertion skin preparation and disinfection of the connections. After 72 h in situ the microbial contamination rate of 580 luers, 306 with standard caps and 274 with needleless connectors attached, was determined. The microbial contamination rate of the external compression seals of 274 needleless connectors was also assessed to compare the efficacy of the three disinfectants. The internal surfaces of 55 out of 306 (18%) luers with standard caps were contaminated with micro-organisms, whilst only 18 out of 274 (6.6%) luers with needleless connectors were contaminated (P<0.0001). Of those needleless connectors disinfected with isopropyl alcohol, 69.2% were externally contaminated with micro-organisms compared with 30.8% disinfected with chlorhexidine/alcohol (P<0.0001) and 41.6% with povidone-iodine (P<0.0001). These results suggest that the use of needleless connectors may reduce the microbial contamination rate of CVC luers compared with the standard cap. Furthermore, disinfection of needleless connectors with either chlorhexidine/alcohol or povidone-iodine significantly reduced external microbial contamination. Both these strategies may reduce the risk of catheter-related infections acquired via the intraluminal route.

Novel approach to investigate a source of microbial contamination of central venous catheters.

The potential route of contamination by skin microorganisms onto the distal tip of central venous catheters during insertion was investigated. Thirty patients undergoing cardiac surgery who required a central venous catheter (CVC) as part of their clinical management were studied. Following catheter placement, the device insertion equipment and the skin at the insertion site were sampled for microorganisms. The distal tips of the CVCs were also sampled in situ within 90 min post insertion. Bacteria were isolated from 20 of 30 (66%) CVC skin insertion sites, from 15 of 30 (50%) guidewires, and from five of 30 (16%) catheter distal tips in situ. These findings suggest that despite rigorous skin disinfection and strict aseptic technique, viable microorganisms are impacted during insertion onto the distal tip of the CVC, which may act as a subsequent nidus of infection.

Guidelines for good practice in central venous catheterization

Central venous catheters (CVC) are commonly used in clinical practice and are associated with several complications, including early and late onset infection. In these guidelines, an outline of good practice for the use of CVC and the prevention of associated infections is presented. Definitions of both localized and systemic catheter-related sepsis are given. Subsequent good practice in relation to the insertion of CVC, including patient preparation, planned duration of catheterization, catheter materials and design of the CVC, are presented. Skin fixation and insertion site care, including the use of dressings and administration sets, as well as an approach to flow obstructions, are also reviewed. The clinical and microbiological diagnosis of catheter-related sepsis and its treatment is next presented. Finally, guidelines for CVC removal and replacement are given. The guidelines are designed to facilitate the development of good practice in the use of CVC, allowing appropriate protocols to be formulated and to reduce infection risk.

Antibiotic-induced release of endotoxin from bacteria in vitro

The ability of cefotaxime, ciprofloxacin, piperacillin and tobramycin to cause release of endotoxin was examined in vitro with cultures of Enterobacter cloacae and Escherichia coli. Endotoxin was measured by a quantitative limulus amoebocyte lysate assay and its presence was confirmed by silver staining of the lipopolysaccharide moiety following SDS-PAGE. The morphology of the bacteria during antibiotic exposure was examined by scanning electronmicroscopy. Cefotaxime, ciprofloxacin and piperacillin caused significant endotoxin release, correlating with their ability to affect cell-wall morphology, causing filamentation, wall breakage and cell lysis. In contrast, little endotoxin was released when bacteria were exposed to tobramycin and no morphological changes were observed when bacteria were exposed to bactericidal concentrations of this aminoglycoside. Its antimicrobial spectrum and bactericidal activity make tobramycin an appropriate agent for treatment of sepsis caused by gram-negative bacteria and its lack of propensity to elicit excessive release of endotoxin may avoid exacerbation of endotoxin-related shock in sepsis.

The effects of electric current on bacteria colonising intravenous catheters

The effect of a direct electric current (10 microA) on the growth of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis was investigated. When the ends of negatively-charged intravascular catheters were placed in nutrient agar seeded with bacteria, circular zones of inhibition of bacterial growth were observed around the catheters. The zones ranged from 6 to 16 mm in diameter according to the organism under test. Zones of inhibition were not produced around positively-charged catheters. Bacteria colonising the surfaces of catheters were similarly affected by the application of a 10 microA electric current. A negative electric current applied to colonised catheters for 4 to 24 h significantly reduced the number of adherent viable organisms as compared to controls. The results demonstrated that a constant electric current of low amperage might be used to reduce bacterial colonisation of intravascular catheters. This may offer a novel means of protecting catheters and other prosthetic devices from associated sepsis in vivo.

Evaluation of PCR in the molecular diagnosis of endocarditis

OBJECTIVE Infective endocarditis (IE) is diagnosed by the Duke criteria, which can be inconclusive particularly when blood cultures are negative. This study investigated the application of polymerase chain reaction (PCR) to identify bacterial DNA in excised valvular tissue, and its role in establishing the diagnosis of IE. METHODS Ninety-eight patients undergoing valve replacement surgery were studied. Twenty-eight patients were confirmed as definite for endocarditis by the Duke criteria; nine were considered as possible and 61 had no known or previous microbial infection of the endocardium. A broad-range PCR technique was used to amplify prokaryotic 16S rRNA genes present within homogenised heart valve tissue. Subsequent DNA sequencing of the PCR amplicon allowed identification of the infecting microorganism. RESULTS PCR results demonstrated the presence of bacterial DNA in the heart valves obtained from 14 out of 20 (70%) definite IE patients with positive blood cultures preoperatively. The causative microorganism for one patient with definite culture negative endocarditis was identified by PCR. Two out of nine (22%) of the valves from possible endocarditis patients also had bacterial DNA present converting them into the definite criteria whereas in the valves of seven out of nine (78%) of these patients no bacterial DNA was detected. CONCLUSION The application of PCR to the explanted valves in patients with possible or confirmed diagnosis can augment the Duke criteria thereby improving post-surgical antimicrobial therapeutic options.