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Background: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital., Methods: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash., Results: A total of 18,810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds sterling), compared with the annual mean for the preceding 6 years. The cost of screening was 302,500 pounds sterling, making a net loss of 26,280 pounds sterling. Compared with 2005, however, there was a net saving of 545,486 pounds sterling., Conclusion: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established., (2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Wound infection in cardiac surgery is a continuing problem despite improvements in surgical technique. The risk factors for, and appearance of, the infected wound differ from operations in other specialties. A robust definition is required for successful surveillance but many are open to different interpretations. At UCLH, comparison between UK and US definitions shows marked differences in patients defined as infected. Surveillance with feedback is effective if conducted over several years, but a high proportion of infected wounds are only identified during post-discharge follow-up. Deteriorating performance of an individual surgeon can be detected and interventions focused on improving faults identified during data collection. Often highlighting the problem is sufficient to reverse the trend, but the process of audit and control is becoming more important as accountability and performance is demanded by primary care providers and patients.

The aim of this study was to demonstrate the use of a graphical method for real-time monitoring of the occurrence of surgical wound infection following cardiac surgery. This included developing and incorporating a risk scoring system so that variations in case-mix could be duly accounted for in the monitoring process. We analysed routinely collected data from a London teaching hospital. These data consisted of records for 2146 patients who had undergone cardiac surgery between April 2000 and March 2004 and whose surgical wounds were followed up as part of the local surveillance programme. The risk model was developed using logistic regression analysis with surgical wound infection diagnosed before hospital discharge as the outcome measure. Factors included in the model were the number of surgical wounds, patient age, operations that combined bypass surgery and valve replacement, renal disease and the number of days between hospital admission and surgery. The model was a good predictor of outcomes recorded within an independent data set (Chi-squared=3.81, P=0.58) and we incorporated it into a graphical tool for monitoring outcomes. The risk model and the associated graphical monitoring method could be valuable tools to assist with infection management. If used in real-time, problems with the care process can be quickly identified allowing timely remedial action to be taken.

Aim: Routine practice in the ICU of University College London (UCL) Hospitals is to use short course (5-6 days) monotherapy, unless contraindicated (e.g. endocarditis, osteomyelitis). The aim of this study is to assess our policy by monitoring the clinical response, relapse rate and patient outcome., Methods: A prospective observational study was carried out from February to July 2000. Clinically significant bacteraemia was identified by daily prospective surveillance of all positive blood cultures. On all the patients we recorded: 1) demographics; 2) antibiotic therapy (type, duration) and ACCP/SCCM sepsis criteria; 3) ICU support techniques (e.g. mechanical ventilation, intravascular catheter changes); 4) development of further bacteraemia or relapses. For all positive results, Gram stain, identification and antibiotic sensitivity patterns were noted. SPSS software was used for statistical analyses., Results: Out of 713 admitted to the ICU over the study period, 84 (8.2%) patients experienced 102 bacteraemic episodes: 14 community-, 28 hospital- and 60 ICU-acquired (occurring in 49 patients). A total of 78 (76.4%) episodes [8 (57%) community-, 22 (79%) hospital- and 48 (80%) ICU-acquired] were treated with short course monotherapy. Moreover a low rate (23.8%) of death directly related to the bacteraemia and a satisfactory (72%) clinical response were recorded. ICU-acquired multidrug resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also uncommon. No patient discharged from the ICU, subsequently developed either bacteraemia relapse, or any long-term related complication., Conclusions: Short course antibiotic monotherapy strategy appears to provide a satisfactory clinical response, low relapse rate and no long-term infectious complications. Multicentre studies are warranted to confirm the efficacy of our practice.

Objectives: To determine the prevalence of teicoplanin and linezolid resistance amongst Gram-positive pathogens isolated in the intensive care unit (ICU) and the impact of any resistance on clinical outcome., Methods: Gram-positive isolates were collected from two critical care units over 1 year. All patients were screened weekly for methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to teicoplanin and linezolid was tested by Etest. The length of hospital and critical care unit stay and the use of antibiotics in each patient were recorded., Results: Reduced susceptibility to teicoplanin (MIC>or=16 mg/L) was found in 21 [3.3% (95% CI 2.0-5.0%) 6 patients] of 643 strains of MRSA versus none of 374 methicillin-susceptible S. aureus (MSSA) [<0.3% (95% CI 0-0.9%)]. Of 49 enterococci 3 were teicoplanin-resistant. All Gram-positive isolates were susceptible to linezolid. The length of treatment with teicoplanin and outcome of patients infected with these strains were similar to that of susceptible strains. MRSA was a more common cause of infection than MSSA but a less frequent colonizer., Conclusions: Resistance to teicoplanin remains at a comparatively low level and there was no clear relationship between susceptibility and outcome in this critically ill population. There was no resistance in Gram-positives to linezolid but this should be kept as a reserve antibiotic to maintain its activity.

Objectives: To determine which method of determining the MIC of teicoplanin produces a result closely related to outcome in the critically ill patient., Methods: Four methods of teicoplanin susceptibility testing-disc diffusion, Etest, VITEK (Legacy and VITEK 2) and agar incorporation-were compared for 47 methicillin-resistant Staphylococcus aureus (MRSA) isolates from invasive intensive care unit (ICU) infections and 83 isolates from ICU patients colonized with the organism. Clinical outcome was recorded prospectively for all the patients. Another 13 reference laboratory strains of MRSA with reduced susceptibility to teicoplanin were tested., Results: Both VITEK systems failed to demonstrate resistance in the three isolates identified as resistant by Etest or agar incorporation, and disc testing detected only one resistant isolate. A higher MIC, as found by Etest or agar incorporation, was associated with lower survival (n = 130, 95% CI -0.082 to -0.006, P = 0.023, Etest; n = 130, 95% CI -0.156 to -0.020, P = 0.011, agar). The findings for the 13 reference strains were similar, with a > or = 4-fold reduction in MIC between agar incorporation or Etest and VITEK2 for six isolates., Conclusions: Neither disc diffusion nor the VITEK systems are reliable for detection of teicoplanin resistance in MRSA. Etest and agar incorporation remain the methods of choice.

Background: Surgical wound surveillance with postdischarge follow-up is rarely done in the UK as it is seen as expensive. The aim of this study was to determine whether employing a dedicated team was effective and reduced costs., Methods: Infection data were collected prospectively with postdischarge follow-up at 2-3 months, and fed back to surgeons. Wound infection was defined using both ASEPSIS wound scoring and criteria of the US Centers for Disease Control (CDC) definitions., Results: Over 4 years, 15 548 patient episodes were included. Postdischarge surveillance data were available for 79.9 per cent of the 15 154 records of patients who survived. There was a significant reduction in the rate of wound infection between the first and fourth years by ASEPSIS and CDC definitions: odds ratio 0.77 (95 per cent confidence interval (c.i.) 0.64 to 0.92) and 0.69 (95 per cent c.i. 0.57 to 0.83), respectively. The proportion of infections fell significantly in orthopaedic, cardiac and thoracic surgery. The annual budget for wound surveillance was pound 91,600. Changes in infection rates contributed pound 347,491 to the reduction in cost among the patients surveyed., Conclusion: Wound surveillance was associated with a reduction in rates of wound infection within 4 years. The cost reduction as a result of fewer infections exceeded the cost of surveillance after 2 years.

The planning and building of new University College London Hospital has provided a challenge to the Infection Control Team to ensure all areas are easy to clean, air flows are correct and appropriate and that there is every opportunity for handwashing. The seven year process illustrates the paper by Stockley et al. ['Stockley JM, Constantine CE, Orr KE, The Association of Medical Microbiologists' New Hospital Developments Project Group. Building new hospitals: a UK infection control perspective.

Few hospitals now launder staff uniforms. Staff are expected to use their own domestic machines, most of which run with 40 degrees C cycles. However, there is little information on the effectiveness of home laundering. This study demonstrates that domestic washing machines reduce viable counts of Staphylococcus aureus to below detectable levels from an inoculum of 10(8)-10(12) colony-forming units (>or=10(6)-fold reduction), even using low temperature (40 degrees C) programmes. Environmental organisms, predominantly Gram-negative flora, were introduced from the machine itself but were destroyed by tumble drying or ironing. Domestic laundering of uniforms is an acceptable alternative to hospital laundering if combined with tumble drying or ironing.

Objectives: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients., Patients and Methods: Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay., Results: A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 +/-0.016 L/h/kg (+/-s.e.m. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09-11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2-127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97+/-1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6-469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died., Conclusions: Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.

Background: Hospital-acquired infection due to meticillin-resistant Staphylococcus aureus (MRSA) is common within intensive-care units. Single room or cohort isolation of infected or colonised patients is used to reduce spread, but its benefit over and above other contact precautions is not known. We aimed to assess the effectiveness of moving versus not moving infected or colonised patients in intensive-care units to prevent transmission of MRSA., Methods: We undertook a prospective 1-year study in the intensive-care units of two teaching hospitals. Admission and weekly screens were used to ascertain the incidence of MRSA colonisation. In the middle 6 months, MRSA-positive patients were not moved to a single room or cohort nursed unless they were carrying other multiresistant or notifiable pathogens. Standard precautions were practised throughout. Hand hygiene was encouraged and compliance audited., Findings: Patients' characteristics and MRSA acquisition rates were similar in the periods when patients were moved and not moved. The crude (unadjusted) Cox proportional-hazards model showed no evidence of increased transmission during the non-move phase (0.73 [95% CI 0.49-1.10], p=0.94 one-sided). There were no changes in transmission of any particular strain of MRSA nor in handwashing frequency between management phases., Interpretation: Moving MRSA-positive patients into single rooms or cohorted bays does not reduce crossinfection. Because transfer and isolation of critically ill patients in single rooms carries potential risks, our findings suggest that re-evaluation of isolation policies is required in intensive-care units where MRSA is endemic, and that more effective means of preventing spread of MRSA in such settings need to be found.

Equine protozoal myeloencephalitis (EPM) is a neurological disease caused by Sarcocystis neurona, an apicomplexan parasite. S. neurona is also associated with EPM-like diseases in marine and small mammals. The mechanisms of transmission and ability to infect a wide host range remain obscure; therefore, characterization of essential proteins may provide evolutionary information allowing the development of novel chemotherapeutics that target non-mammalian biochemical pathways. In the current study, two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry were combined to characterize and identify an enolase protein from S. neurona based on peptide homology to the Toxoplasma gondii protein. Enolase is thought to be a vestigial, non-photosynthetic protein resulting from an evolutionary endosymbiosis event of an apicomplexan ancestor with green algae. Enolase has also been suggested to play a role in parasite stage conversion for T. gondii. Characterization of this protein in S. neurona and comparison to other protozoans indicate a biochemical similarity of S. neurona enolase to other tissue-cyst forming coccidians that cause encephalitis.

Objective: As optimal antibiotic therapy for bacteraemia remains unknown, different strategies have evolved. Routine practice in the University College London Hospitals intensive care unit (ICU) is to use short-course (5-6 days) monotherapy, unless specifically indicated (e.g. endocarditis, osteomyelitis). We decided to assess this approach for treating community-, hospital-, and ICU-acquired bacteraemia by monitoring clinical response, relapse rate and patient outcome., Design: Six-month prospective observational study from February to July 2000., Setting: Mixed medical-surgical tertiary referral ICU., Patients: All 713 patients admitted to the ICU over the study period., Measurements and Results: In total, 102 bacteraemic episodes occurred in 84 patients. Eight (57%) of 14 community-acquired bacteraemias, 22 (79%) of 28 hospital-acquired bacteraemias, and 48 (80%) of 60 ICU-acquired bacteraemias (in 49 patients) were treated with short-course monotherapy. Compared with previous reported studies, these patients had a low rate (23.8%) of death directly attributable to the bacteraemia and a satisfactory clinical response in 72%. Of six relapses (all Gram-negative), four had received combination therapy for severe deep-seated infections. ICU-acquired multidrug-resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also uncommon. No patient discharged from ICU subsequently developed a new bacteraemia relapse, or any long-term complication such as osteomyelitis., Conclusions: Our general strategy of short-course antibiotic monotherapy for treating bacteraemia in the critically ill appears to provide a satisfactory clinical response, low relapse rate and no long-term complications in a well-defined group of patients. Multicentre studies are warranted to compare short versus long course therapy, and monotherapy versus combination therapy.

Objective: To assess the level of agreement between common definitions of wound infection that might be used as performance indicators., Design: Prospective observational study., Setting: London teaching hospital group receiving emergency cases as well as tertiary referrals., Participants: 4773 surgical patients staying in hospital at least two nights., Main Outcome Measures: Numbers of wound infections based on purulent discharge alone, on the Centers for Disease Control (CDC) definition of wound infection, on the nosocomial infection national surveillance scheme (NINSS) version of the CDC definition, and on the ASEPSIS scoring method., Results: 5804 surgical wounds were assessed during 5028 separate hospital admissions. The mean percentage of wounds classified as infected differed substantially with different definitions: 19.2% with the CDC definition (95% confidence interval 18.1% to 20.4%), 14.6% (13.6% to 15.6%) with the NINSS version, 12.3% (11.4% to 13.2%) with pus alone, and 6.8% (6.1% to 7.5%) with an ASEPSIS score > 20. The agreement between definitions with respect to individual wounds was poor. Wounds with pus were automatically defined as infected with the CDC, NINSS, and pus alone definitions, but only 39% (283/714) of these had ASEPSIS scores > 20., Conclusions: Small changes made to the CDC definition or even in its interpretation, as with the NINSS version, caused major variation in estimated percentage of wound infection. Substantial numbers of wounds were differently classified across the grades of infection. A single definition used consistently can show changes in percentage wound infection over time at a single centre, but differences in interpretation prevent comparison between different centres.

The infecting pathogen and its susceptibility to antibiotics is used to suggest prognosis in endocarditis. A case study was performed in a tertiary referral cardiology centre to assess the contribution of the measurement of minimum inhibitory concentration (MIC) to the decision to treat endocarditis surgically. The records were examined of 125 patients admitted between 1981 and 1999 in whom the minimum inhibitory concentration for the pathogen had been measured. The measures of outcome were mortality at time of hospital discharge and at 6 months, surgical referral and cure by medical treatment. Endocarditis caused by Staphylococcus aureus with a raised MIC of flucloxacillin (methicillin) was associated with higher mortality even if glycopeptides were used in treatment (< or = 35 mg/l 0/7 versus MIC 1-2 mg/l 4/13, P = 0.01). Elevated MICs of flucloxacillin in S. aureus infection or of gentamicin in streptococcal disease were associated with surgical intervention. There were no significant differences between bacterial pathogens in mortality, surgical referral or cure by medical treatment. The measurement of MIC appears prognostically important in deciding the surgical management of endocarditis.

Objectives: Linezolid, the only commercially available oxazolidinone, is indicated for the treatment of Gram-positive infections, although little has been published specifically on its use in the critically ill. A randomized, prospective study was therefore performed to compare linezolid with the glycopeptide antibiotic, teicoplanin, for the treatment of suspected or proven Gram-positive infections in an intensive care population., Methods: Using a double-blind, double-dummy, prospective design, patients were randomized to (i) intravenous linezolid (600 mg/12 h) plus teicoplanin dummy [one dose/12 h for three doses then every 24 h intravenously (iv)] or (ii) teicoplanin (400 mg/12 h for three doses then 400 mg/24 h iv) plus linezolid dummy (one dose/12 h iv). Other antibiotics were used in combination with the trial agents in empirical treatment. Clinical and microbiological assessments were made daily in the first week, and at 8 and 21 days after treatment., Results: One hundred patients received linezolid plus placebo-teicoplanin, whereas 102 received teicoplanin plus placebo-linezolid. Population baseline characteristics were similar in both groups. At end of treatment, clinical success [71 (78.9%) linezolid versus 67 (72.8%) teicoplanin] and microbiological success [49 (70.0%) versus 45 (66.2%)] rates were similar, as were adverse effects, intensive care unit mortality, and success rates at short- and long-term follow-up. Linezolid was superior at initial clearance of methicillin-resistant Staphylococcus aureus (MRSA) colonization (end of treatment, 51.1% versus 18.6%, P = 0.002). Two MRSA isolates showed reduced susceptibility to teicoplanin., Conclusions: Linezolid has similar safety and efficacy to teicoplanin in treating Gram-positive infections in the critically ill. Short-term MRSA clearance achieved with linezolid suggests better skin and mucosal penetration.

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in intensive care units in most countries. Despite recommendations for screening and isolation of patients with MRSA our perception has been that there is little uniformity in approach in ICUs besides adherence to basic infection control procedures. We thus sought to identify MRSA prevalence and the variation of infection control policy across intensive care units in England., Design and Setting: Postal questionnaire with telephone follow-up in English intensive care units., Measurements and Results: Responses were obtained from 217 (96%) ICUs. Marked variation in practice was noted in terms of patient screening, staff screening, infection control procedures, isolation or cohorting of colonised/infected patients, and ward discharge policy. Point prevalence data showed that 16.2% of ICU patients were known to be colonised or infected with MRSA. There was a regional bias, but no difference was noted between high and low prevalence regions in terms of unit demographics or infection control policies., Conclusions: This study highlights the lack of consistent policy across English ICUs regarding isolation, screening and discharge practices for MRSA. Prospective studies are urgently needed to determine best practice.

Objectives: To determine the variability of prostate-specific antigen (PSA) in the breast ductal fluid (nipple aspiration fluid, NAF) during the menstrual cycles of healthy premenopausal women., Methods: Fifteen female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts for the duration of two menstrual cycles. A highly sensitive and specific Third Generation PSA Assay (IMMULITE); Diagnostic Products Corporation, DPC) was used to detect NAF and serum PSA. Associations between NAF PSA and paired serum hormone levels of the pituitary-ovarian axis were tested using the Spearman rank correlation and the Wilcoxon signed rank test. Analysis of variance on log transformed NAF PSA was used to determine the intra- and intervolunteer variability., Results: NAF PSA ranged from <0.003 to 133,330 ng PSA/g total protein (median 2,030 ng/g). No repeatable pattern of change was observed for individual volunteers and no significant association between NAF PSA and any pituitary-ovarian axis serum hormone was detected. There was no correlation between serum and NAF PSA., Conclusions: Weekly NAF sampling in healthy premenopausal women to provide adequate volumes for PSA analysis was successfully achieved. Considerable variation was observed for NAF PSA, which may limit the future potential for this tumor marker in NAF. This variability was not associated with hormones of the pituitary-ovarian axis and did not show repeated cyclical variability during the menstrual cycle. Serum PSA does not appear to be an acceptable indicator of NAF PSA levels., (Copyright 2002 S. Karger AG, Basel)

Objective: To identify clinical markers available within the first 48 hours of admission that are associated with poor outcome in infective endocarditis., Designs: Retrospective cohort study., Setting: Teaching hospital., Patients: 208 of 220 patients with infective endocarditis., Methods: Consecutive patients with infective endocarditis presenting between 1981 and 1999 to a tertiary centre were studied. Clinical, echocardiographic, and haematological data recorded within 48 hours of admission were obtained. Data were analysed using logistic regression models., Main Outcomes Measures: Mortality at discharge and at six months., Results: Data were obtained for 93% of patients who were eligible for inclusion. 194 (93%) were positive for Duke criteria. Mean age was 52 (1.2) years, and 138 (66%) were men. 82 (39%) were transferred from other hospitals. 181 (87%) were blood culture positive, and 47 (23%) infections were Staphylococcus aureus. The infection was located on aortic (n = 85, 41%), mitral (n = 77, 37%), tricuspid (n = 18, 9%), and multiple valves (n = 20, 10%). 67 (32%) had prosthetic valve endocarditis. 48% of the cohort were managed with antibiotics alone. Mortality at discharge was 18% and at six months 27%. Duration of illness before admission, age, sex, valve infected, infecting organism, and left ventricular function were not predictors of adverse mortality. However, abnormal white cell count, serum albumin concentration, serum creatinine concentration, or cardiac rhythm, the presence of two major Duke criteria, or visible vegetation conferred a poor prognosis., Conclusions: Conventional prognostic factors in this study did not appear to predict outcome early during hospital admission. However, simple clinical indices, which are readily available, are reliable, cheap, and potentially powerful predictors of poor outcome.

Infections are unusual following minimally invasive surgery but antibiotic prophylaxis is given in the same way as for the open surgery equivalents. Most prophylactic regimens have not been subjected to randomised placebo controlled trials. Antibiotic prophylaxis has been shown to be beneficial in transurethral resection of the prostate. In endoscopic retrograde cholangiopancreatography (ERCP) the incidence of bacteremia, but not cholangitis, is reduced by prophylaxis and some do not recommend its routine use. For arthroscopies and laparoscopies infection is too rare to warrant prophylaxis. There is a theoretical risk of infection in that endoscopes cannot withstand autoclaving so only high level disinfection can be used between patients. However, for most minimally invasive operations, the small wound size, reduced immune challenge and rapid recovery of the patient outweigh any disadvantages compared with open surgery.

Idiopathic scoliosis is a highly prevalent disorder, familial in nature, with marked clinical variability. The purpose of this study was to characterize idiopathic scoliosis in a large series of families to be used for a genome-wide search. One hundred thirty-one multigenerational families (892 individuals) with at least two affected individuals were studied. Data obtained included curve pattern, treatment, and back pain. Maximum curvature as a continuous variable was evaluated using t tests for dichotomous characteristics and linear correlation for continuous variables. An analysis of familial loading was done. Four hundred forty-four individuals were classified as affected (82% female; 18% male). The right thoracic and left lumbar curves had the highest mean curvature (49 degrees). Mean curve size was greater in individuals with back pain. Back pain was most prevalent in the right thoracic and left lumbar curve pattern. The Pearson correlation coefficient between the number of affected family members and the maximum degree of curvature was 0.16, suggesting that the greater the lateral curvature, the higher the proportion of family members affected with scoliosis. The sample population is consistent with those of previous studies in relation to gender and curve size. Statistically, the familial nature of this disorder is supported.

Sitafloxacin is a new quinolone active against multi-resistant Gram-positive pathogens. An open study was conducted in patients with serious systemic infections with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE). Patients with MRSA were recruited if treatment with glycopeptides had failed. Of 11 patients with MRSA infection, four were cured, six failed treatment and one was indeterminate. Of nine patients with VRE infection (one patient had both pathogens), five were cured and four failed. Fifteen adverse events in 12 patients were potentially related to the study drug. Sitafloxacin was effective in VRE and some recalcitrant MRSA infections.

The glycopeptide antibacterial teicoplanin has become increasingly popular in the last decade with the rise in infections related to methicillin-resistant Staphylococcus aureus. Teicoplanin has 6 major and 4 minor components. It is predominantly (90%) bound to plasma proteins. Of the several methods available to measure concentrations in serum, fluorescence polarisation immunoassay has high reliability and specificity. Teicoplanin is not absorbed orally, but intravenous and intramuscular administration are well tolerated. Teicoplanin is eliminated predominantly by the kidneys and only 2 to 3% of an intravenously administered dose is metabolised. Total clearance is 11 ml/h/kg. Steady state is reached only slowly, 93% after 14 days of repeated administration. Elimination is triexponential, with half-lives of 0.4 to 1.0, 9.7 to 15.4 and 83 to 168 hours. Volumes of distribution are 0.07 to 0.11 (initial phase), 1.3 to 1.5 (distribution phase) and 0.9 to 1.6 (steady state) L/kg. A standard dosage regimen of 6 mg/kg every 12 hours for 3 doses, then daily, will produce therapeutic serum concentrations of > or = 10 mg/L in most patients. Higher dosages may be required in certain patients, for example intravenous drug abusers or those with burns, because of unpredictable clearance. Concentrations in bone reach 7 mg/L at 12 hours after a dose of teicoplanin 6 mg/kg, but reach only 3.5 mg/L in the cartilage. Doses of 10 mg/kg are necessary to achieve adequate bone concentrations. There is little penetration into cerebrospinal fluid or the aqueous or vitreous humour. In fat, concentrations may be subtherapeutic (0.5 to 5 mg/L) after a dose of 400mg. A single prophylactic dose of 12 mg/kg is sufficient to maintain therapeutic concentrations during cardiopulmonary bypass or burns surgery. High loading doses reduce the delay to attaining therapeutic concentrations. Premature neonates require a loading dose of 15 mg/kg and a maintenance dosage of 8 mg/kg daily to ensure therapeutic serum concentrations. Children need loading with 10 mg/kg every 12 hours for 3 doses followed by maintenance with 10 mg/kg/day. Clearance is reduced predictably in renal failure, and dosage adjustments can be based on the ratio of impaired clearance to normal clearance. In patients on haemodialysis, 3 loading doses of 6 mg/kg at 12-hour intervals followed by maintenance doses every 72 hours produced trough plasma concentrations of 8 mg/L in most patients at 48 hours. The monitoring of serum concentrations is not necessary to avoid toxicity, but can be helpful in certain patient groups to ensure therapeutic concentrations are present, especially in those not responding to treatment.

Falciparum malaria can cause immune suppression sufficient to allow opportunistic infection during the recovery phase. A patient is described who died from a disseminated infection with Aspergillus flavus and Absidia corymbifera, unresponsive to treatment with amphotericin and voriconazole.

Improvements in the treatment of compromised patients have resulted in their prolonged survival in a debilitated state. Patients have repeated courses of antibiotics and become colonised with multiresistant pathogens during a stay in the intensive care unit. Surgical wound infections can then be very difficult to treat. Methicillin-resistant Staphylococcus aureus is now common although wide variations in prevalence exist between countries and regions. Klebsiella spp with multiple resistance is a common cause of septicemia and can be associated with cephalosporin use. Acinetobacter spp and vancomycin-resistant enterococci can cause infections resistant to all readily available antibiotics. The prevalence of infection with each of these pathogens is increasing. Control measures should include hand washing, universal precautions for infection control, source isolation, restrictive antibiotic policy and antibiotic rotation. Although new agents currently in trials may be effective in the long term, the future for antibiotic treatment or prophylaxis of surgical infections is in doubt.

The cytotoxic effect of conifer Tetraclinis articulata essential oil (TAEO) on a number of human cancer cell lines and peripheral blood lymphocytes was assessed at various concentrations and time exposures. The cytotoxic effect showed the hallmarks of apoptosis confirmed by a variety of techniques including flow cytometry, an apoptosis- specific marker combined to fluorescent staining and DNA laddering. All cell lines tested were inhibited in a dose-dependent fashion and within a contact time of less than eight hours for the higher concentrations. Melanoma, breast and ovarian cancer cells gave IC50s of around 80 micrograms/ml whilst the IC50s on peripheral blood lymphocytes was almost double this value. We conclude that the essential oil contains components that are effective at inducing apoptosis. The advantages of using a mixture of monoterpenes (C10) as present in an EO over a single component, are discussed.

Background: The array of antibodies and assay formats utilised by kit manufacturers contribute to different values being quoted as clinically "normal". Kit-specific reference range limits will maximise the clinical utility of tumour marker assays., Materials and Methods: Serum samples (approximately 800) were obtained from volunteers, age 20-70 years, in France, Germany, The Netherlands and Portugal. Each sample was assayed with a number of DPC tumour markers kits. IMMULITE assays were carried out in The Netherlands; Coat-A-Count IRMA, IRMA-Count, Double Antibody and Milenia assays at EURO/DPC Ltd. Analytes included, BR-MA, OM-MA, GI-MA (for the determination of CA 15-3, CA 125 and CA 19-9, respectively), CEA, PSA, PAP and HCG., Results: The median and 95th percentiles for each analyte in each assay format were estimated; where appropriate, data subsets were considered., Conclusion: Kit-specific reference range data generated for important tumour marker analytes will help clinicians interprete their assay results.

Intraoperative bacteraemia has been used as an indicator of the efficacy of prophylactic antibiotics. Two clinical isolates of Staphylococcus aureus in nutrient broth, with or without human serum, were exposed to teicoplanin (50 mg/L) and, either immediately or after 30 min, inoculated into blood culture bottles. Bottles with and without resin were used and the experiment was repeated five times with one strain. In the absence of teicoplanin, an inoculum of 10 cfu/mL produced growth in both resin and non-resin bottles. In the presence of teicoplanin, an inoculum of at least 10(5) cfu/mL was required in non-resin bottles to obtain growth, but this was reduced to 10(2)-10(3) cfu/mL for resin bottles. Intraoperative blood cultures overestimate the efficacy of bacterial killing by prophylactic antibiotics during surgery.

Accurate information on the prevalence of surgical wound infection is difficult to obtain; outpatient follow-up is often inadequate. For two months in 1993 and again in 1995, surgical wounds throughout one hospital were examined by the same observer with the intention of comparing different methods for assessing wound infection. Two standard definitions [Centers for Disease Control (CDC), USA and National Prevalence Survey (NPS), UK] were compared with ASEPSIS and the Southampton method. In 1993, 325 wounds in 230 patients were examined with follow-up of 203 (88%) patients. In 1995, 559 wounds were surveyed in 375 patients with follow-up in 364 (97%). Patient groups in the two years were similar. ASEPSIS identified 92 (13%) wounds as having scored over 20 points indicating infection, and another 16.5% having disturbance of healing. There was no significant difference between the two surveys. The two scoring methods were more sensitive than the standard definitions but CDC and NPS did not differ significantly from each other. Between 44 and 47% of clean wounds identified as infected by standard definitions were classed as disturbance of healing by ASEPSIS. All methods were labour-intensive and to implement any one of them on a regular basis would require a full-time investigator. The first surveillance program with feedback of results to the surgeons did not significantly affect the rates two years later.

Teicoplanin have different safety profiles which can affect choice. Nephrotoxicity is significantly less likely to occur during treatment with teicoplanin than vancomycin when an aminoglycoside is being given concurrently. 'Red man' syndrome is a troublesome effect of vancomycin infusion which is extremely uncommon with teicoplanin use. Rash and fever can be dose-related phenomena but patients reacting to one glycopeptide may not react to both. Although thrombocytopenia is more frequent with teicoplanin, it is reversible and seldom seen at standard doses.

Attachment of coagulase-negative staphylococci to plastic surfaces by means of hydrophobic interaction and slime production may be important in producing catheter associated infections. In continuous ambulatory peritoneal dialysis (CAPD), the relationship between these properties and disease is unclear and the effect of dialysate fluid is not considered. For a collection of coagulase-negative staphylococci from CAPD patients, slime production and adherence were measured by colorimetric methods and hydrophobicity was determined by autoaggregation in ammonium sulphate solution. Comparison of 73 nasal isolates with 69 isolates from peritonitis showed no significant differences with respect to three properties, with the exception of a greater adherence of peritoneal isolates in dialysate because of a greater proportion of staphylococcal species other than Staphylococcus epidermidis. Fewer strains showed adherence in dialysate (12/142 8.5%) than in broth (94/142 66%) but the proportion of strains producing slime was similar. The milieu of the bacteria rather than the organisms themselves may be of greater importance in the establishment of infection.

Background: Clinical deterioration after burn wound manipulation may be related to the release of cytokines including tumour necrosis factor-alpha (TNF) and interleukin-6 (IL-6)., Methods: The two cytokines were assayed by immunoenzymetric assay in blood samples taken before and during manipulation of the burn wound. An antibiotic, teicoplanin, was administered to half the patients at the start of the procedure in a randomized fashion as part of a separate trial., Findings: Sixty patients with a median burn size of 8% (range 1-56%) were studied during dressing change (n = 40) or burn excision (n = 20). There was little change in TNF levels between preoperative and recovery samples but IL-6 concentrations increased three-fold, particularly in those with large recent burns or bacteraemia, and were correlated with poor clinical outcome. The presence of teicoplanin did not significantly affect the levels of either cytokine., Interpretation: The systemic cytokine response to burn wound dressing or debridement is predominantly that of IL-6 and it is not significantly reduced by preventing Gram-positive bacteraemia during the procedure.

Background: Burn wound surgery or change of dressings commonly causes bacteraemia. The use of antibiotic prophylaxis has not been tested adequately in a controlled trial., Methods: A randomized double-blind placebo-controlled study was performed to determine the effect on Gram-positive bacteraemia and clinical outcome of a single dose of teicoplanin (12 mg/kg intravenously) given at burns surgery or change of dressings., Results: A total of 134 patients were entered into the study, representing 220 episodes of dressing or debridement (110 episodes in each group). There was a significant difference between the groups with respect to perioperative Gram-positive bacteraemia: eight episodes (7 per cent) in the teicoplanin group versus 51 (46 per cent) in the placebo group (P < 0.001). However, good clinical outcome was similar in both groups (80 of 110 versus 77 of 110 respectively, P = 0.7). Only eleven patients had bacteraemia caused by Gram-negative species alone. Bacteriological response in terms of wound culture showed no significant difference between the groups: 63 (57 per cent) of 110 episodes versus 58 (53 per cent) of 110 respectively respectively., Conclusion: Prevention of Gram-positive bacteraemia did not affect postoperative recovery.

Exit site infection is a major risk factor for the development of peritonitis in continuous ambulatory peritoneal dialysis. The frequency of infection can be reduced by scrupulous exit site care with or without topical antiseptics. A randomized trial was performed of 149 catheters in 130 patients to assess any additional benefits conferred by the use of povidine iodine dry powder spray at dressing changes over an existing strict protocol of exit care. Exit infections occurred in 14 (18%) of 77 patients using spray and in 15 (21%) of 72 patients not using spray. The risk of peritonitis was also similar in each group. The proportion of infections caused by Staphylococcus aureus was reduced in the spray group, but those caused by Pseudomonas aeruginosa were increased. Rash occurred in 6% of those using the spray. The use of the spray did not therefore seem justified.

Antibiotic treatment of patients developing infection after burns is principally based on experience with other surgical patients. Few comparative trials have been performed in burns patients despite the altered pharmacokinetics of antibiotics and the high incidence of Gram-positive infection in the first week. A randomized trial was performed to compare the cure rates of presumed Gram-positive infection in burns patients given teicoplanin (6 mg/kg every 12 h for three doses then daily) or flucloxacillin (1 g every 6 h i.v./p.o.). Both groups received gentamicin if additional Gram-negative infection was thought likely. A total of 64 patients were entered into the study representing 65 episodes of treatment of which 55 were completed. Clinical success was achieved in 22 (73%) of 30 evaluable patients given teicoplanin and in 21 (68%) of 31 evaluable patients given flucloxacillin (not significant). Of 51 patients assessable for bacteriological efficacy, clearance was achieved in 15 (63%) of 24 patients given teicoplanin and in 15 (56%) of 27 patients given flucloxacillin (not significant). Serum trough concentrations of teicoplanin were 9 mg/L in five patients at the steady state. Adverse events were recorded in 15 (48%) of episodes in the teicoplanin group and in 14 (41%) of episodes in the flucloxacillin group. Teicoplanin demonstrated similar efficacy and safety to flucloxacillin with or without gentamicin.

Infective endocarditis is an uncommon disease but retains a high mortality. Glycopeptides are used for patients with resistant pathogens, those allergic to penicillins or for those outside the hospital. The once daily administration of teicoplanin and its low toxicity suggest that it would be suitable for use in the long courses required for endocarditis. However, the dosage and combinations to be used require further study. A retrospective review has been made of 104 episodes of endocarditis treated with teicoplanin in 101 patients seen over 7 years. Most patients had been referred to major London hospitals following failure of medical treatment. After three loading doses of 400 mg, teicoplanin was given at a dose of 400 mg/day in combination with other antibiotics such as gentamicin. Follow up was for one year. The most common pathogens were Streptococcus sanguis (15 cases), Staphylococcus aureus (13 cases) and Staphylococcus epidermidis (10 cases). Of 80 patients febrile at the start of treatment with teicoplanin, 63 (79%) lost their fever within a median of 2 days (1-35 days). Cure without surgery was effected in 50 (48%) and 75% of patients survived. Other antibiotics, usually gentamicin or rifampicin, were used in 92 (90%) of patients. Two strains of Streptococcus spp. were said to be resistant but there was no relationship between MIC of teicoplanin and outcome. Pathogens with a high MBC tended to be more likely to resist treatment. Adverse effects resulted in the withdrawal of teicoplanin in 20 cases (19%) but most events were mild and renal deterioration occurred in only five patients. Teicoplanin was effective in the treatment of endocarditis and appeared to be safe given the severity of disease in the patients treated.

Two monoclonal antibodies (ME1 and ME2), which recognise both normal mesothelial cells and mesothelioma were used in conjunction with AUA1, an antibody with epithelial specificity, against a panel of five cultured human mesothelial cell lines and seven human epithelial ovarian cancer cell lines. Neither antibody was totally specific for mesothelial cells or ovarian tumour cell lines, but the combination of ME1/ME2 and AUA1 was more useful for positive identification. All mesothelial cell lines and no ovarian tumour cell lines were AUA1-/ME1+. The tumour cell lines showed one of three combinations; AUA1+/ME1- (4/7), AUA1+/ME1+ (2/7), AUA1-/ME1- (1/7). It is suggested that the combination of AUA1 and ME1 allows positive identification of mesothelial cells in culture, and that their use may have a role in identifying phenotypic changes associated with the development of ovarian malignancy from surface epithelium of the ovary.

The diagnosis and treatment of burn wound infection is commonly determined by clinical impression and the qualitative results of surface swabs. It has been suggested that quantitative bacteriology from burn wound biopsies confirms burn wound infection and improves patient management. Methods for quantitating surface flora have been described, but comparisons with biopsy specimens have been contradictory. The quantitative and qualitative results of 141 pairs of biopsies and surface swabs, from 74 burn patients, were compared. Staph. aureus was the commonest organism isolated (29 per cent of biopsies and 35 per cent of swabs). Recovery of the same set of species from biopsy and swab occurred in 54 per cent of pairs. There was a significant correlation between the bacterial count obtained by biopsy and by surface swab (P < 0.001), but using various threshold values, the predictive value of the counts obtained by one method to predict the counts obtained by the other was poor. Parallel cultures taken on 18 occasions, showed a significant correlation between bacterial counts obtained from two biopsies or two swabs taken simultaneously (P < 0.002), but there was wide variation in bacterial densities from the same burn wound at the same time. Recovery of the same set of species from both biopsies occurred in 56 per cent of pairs, and from both swabs in 50 per cent of pairs. The use of quantitative microbiology in burns is limited by the unreliability of a single surface swab or biopsy to represent the whole burn wound.

The use of quantitative bacteriology in the burns unit has been thought to be efficient in predicting sepsis or graft loss. To examine the relationship between clinical outcome and bacterial densities on and in the burn wound, 69 biopsy/surface swab pairs were collected from 47 patients on 64 occasions, either immediately prior to excision and grafting, or at routine change of dressings. The mean per cent TBSA burn was 16 (range 1-65). There was a significant correlation between log total bacterial count by biopsy with total white cell count and age (P = 0.028), and a significant negative correlation between total bacterial count by swab with per cent TBSA (P = 0.006). There was no significant difference in bacterial counts between patients judged to be a clinical success or clinical failure (72 h follow-up), either after undergoing excision and grafting, or change of dressings, and no difference in counts between patients with perioperative bacteraemia and those without. With burns > 15 per cent TBSA, a relationship between bacterial counts and subsequent sepsis or graft loss still was not demonstrated. It is suggested that quantitative bacteriology by burn wound biopsy or surface swab does not aid the prediction of sepsis or graft loss.