The in-vitro activity of povidone-iodinecream against Staphylococcus aureus and its bioavailability in nasal secretions.

Due to the emergence of mupirocin-resistance in some epidemic strains of methicillin resistant Staphylococcus aureus (EMRSA) and the appearance of EMRSA with intermediate resistance to vancomycin, we evaluated the in-vitro activity of 5% povidone-iodine ('Betadine') cream as a possiblealternative to mupirocin for the elimination of nasal carriage of S. aureus. As judged by enrichment culture, povidone-iodine was bactericidal against three mupirocin-sensitive strains of S. aureus from nasal carriers, and against mupirocin-resistant and -sensitive strains of EMRSA types 3, 15 and 16, after incubation with povidone-iodine for 1.0 min at 32 degrees C. Mupirocin nasal ointment did not prevent growth after 180 min incubation. In a quantitative suspension test, 1:100 dilution of povidone-iodine cream completely eliminated an inoculum of 10(8)cfu/mL of all nine test organisms after incubation at 32 degrees C for 1.0 min, and 1:1000 dilution reduced cfu, by a factor of 10(5). After direct inoculation of the povidone-iodine cream to give 10(5)cfu/g, none of the test strains were recoverable after 30 s, giving a killing rate of approximately 10(4)cfu/s; for mupirocin nasal ointment, the maximum reduction of mupirocin-sensitive strains was ten fold after 3 h. Povidone-iodine activity was not detectable in sensitivity-testing agar, although 0.025% of povidone-iodine was detectable in a 15% nutrient strength tryptone soya agar. Using this minimal medium, the addition of nasal secretions (from any of 11 samples) reduced the activity of povidone-iodine by 80-90%, but mupirocin activity was unaffected. One millilitre of nasal secretions inactivated the equivalent of approximately 22.5 mg of povidone-iodine. These results suggest that povidone-iodine cream may have a role in the prevention of colonization and infection caused by MRSA, including mupirocin-resistant strains.

The nose: an underestimated source of Staphylococcus aureus causing wound infection.

For the last fifty years, the nose has been intermittently recognized and targeted as a source of Staphylococcus aureus causing surgical site infection. In London in 1959, Williams and co-workers established for the first time that nasal carriers had increased rates of surgical sepsis compared with non-carriers. For half of these patients, the source was the patient's own nose. Post-admission acquisition of tetracycline-resistant strains was associated with even higher rates of infection. The increasing appearance of epidemic methicillin-resistant S. aureus (MRSA) in the 1980s rekindled interest in these (largely overlooked) studies, when the elimination of nasal carriage by topical mupirocin proved pivotal for the control of MRSA in Northern Europe and elsewhere. In the late 1980s and 1990s, Boelaert, Holton and others, appreciating the work performed forty years previously, used nasal mupirocin for the successful prevention of sepsis with S. aureus in patients on haemodialysis and continuous ambulatory peritoneal dialysis without incurring problems with mupirocin resistance. In 1995, Kluytmans and colleagues demonstrated that nasal carriage of S. aureus is a significant risk factor for wound infection after cardiac surgery. Towards the year 2000, the use of prophylactic nasal mupirocin for the prevention of serious sepsis in major clean surgery is emerging as a plausible and exciting new strategy.

Identification and antibiotic susceptibility of Nocardia farcinica and N. nova in the UK.

Nocardia asteroides has long been recognised as a heterogeneous group of organisms. The description and identification of two new subgroups, N. farcinica and N. nova, in other countries encouraged us to re-examine a collection of N. asteroides isolates from the UK. Of 73 clinical isolates identified as N. asteroides from different parts of England and Wales during 1991-1993, and now subjected to further differentiation tests by the Mycobacterial/Nocardial Reference Laboratory, 15 (20.5%) were identified as N. farcinica based on three out of four characteristics: growth property, acetamide production, rhamnose assimilation and a distinct antibiogram. No isolates were identified as N. nova. A revised identification and susceptibility system has significant clinical and taxonomic implications. Its introduction will improve speciation, identify antibiotic resistance and influence the choice of safer alternative therapy for patients infected with Nocardia spp. in the UK.

Bactericidal and inhibitory activity of quinupristin/dalfopristin against vancomycin- and gentamicin-resistant Enterococcus faecium.

There is a need for new agents, or combinations of agents, for the treatment of infections caused by vancomycin- and gentamicin-resistant Enterococcus faecium (VGREF) that may be resistant to all available antimicrobial agents. The early in-vitro activity of quinupristin/dalfopristin (30:70)--an injectable streptogramin--encouraged us to test this agent against VGREF. By broth dilution, the MICs of quinupristin/dalfopristin against 38 isolates of VGREF ranged from 0.06 mg/L to 2.0 mg/L (mode 0.12 mg/L). The addition of 0.5 mg/L of ciprofloxacin significantly reduced the modal MIC of quinupristin/dalfopristin to 0.015 mg/L (P = 5.75 x 10(-8)). Although the addition of 8.0 mg/L of teicoplanin or 4 mg/L of tetracycline did not significantly reduce the modal MIC, the lowest concentration of the MIC range was reduced from 0.06 to 0.015 mg/L. In broth, quinupristin/dalfopristin had slow bactericidal activity against the four strains tested over 48 h, with a 1-2 log10 cfu/mL reduction after 24 h in > 1 mg/L of quinupristin/dalfopristin for two strains and > 8 mg/L for the two other strains. A mixture of quinupristin/dalfopristin in a 70:30 ratio was more bactericidal: against one of the four strains 4-32 mg/L of the combination produced a further 0.5-1.0 log10 reduction in cfu/mL after 24 h and there was a reduction of 6.0 log10 cfu/mL after 48 h for another. By ultracentrifugation, the binding of 32 mg/L quinupristin/dalfopristin to human plasma protein was 90%, and in plasma broth, 32 mg/L of quinupristin/dalfopristin maintained bacteriostatic but not bactericidal activity. There is some useful synergy with ciprofloxacin and tetracycline, and the activity of quinupristin/dalfopristin may be enhanced against some strains by reversing the concentrations of its two components, quinupristin and dalfopristin, as that may occur in vivo.

Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure.

The efficacy of prophylactic parenteral antibacterials, with or without selective decontamination of the digestive tract, was compared in patients with acute liver failure (ALF) or severe acetaminophen hepatotoxicity. One hundred eight patients were randomized on admission to receive intravenous ceftazidime and flucloxacillin, plus either oral and enteral decontamination with colistin, tobramycin, and amphotericin B (group 1), or enteral amphotericin B alone (group 2). The two groups were comparable with respect to age, gender, etiology, coma grade on admission, international normalization ratio, presence of renal failure, Acute Physiology and Chronic Health Evaluation II score, and indicators of poor prognosis. Patients were monitored for clinical and microbiological evidence of infection. There were 15 episodes of infection in 10 of 47 patients (21%) in group 1 and 17 episodes in 12 of 61 patients (20%) in group 2. No differences in incidence, site, and causative organisms of infection were observed between the two groups. Overall, the incidence of infection was significantly higher in patients who developed encephalopathy than in those who did not. In patients who on arrival were not encephalopathic, the development of infection was associated with progression to coma. Duration of Liver Intensive Care Unit (LICU) stay was an independent risk factor for the development of infection. Parenteral antibiotics are effective at reducing the risk of infection in patients with ALF; enteral decontamination provided no additional benefit.

Serious infections caused by multiply-resistant Enterococcus faecium.

Three liver transplant patients developed serious intraabdominal infections and recurrent bacteremias due to strains of Enterococcus faecium with high-level resistance to vancomycin. The enterococci were also resistant to all other antibacterials except pristinamycin, which, given orally, proved ineffective. One strain was sensitive to tetracycline. Increasingly, clinicians are likely to encounter infections caused by multiply-resistant enterococci, and these cases illustrate the seriousness of such infections in compromised patients.

Activity of sucralfate (sucrose octa-sulphate), an anti-ulcer agent, against opportunistic gram-negative bacilli.

The in-vitro activity of sucralfate (sucrose octa-sulphate) in suspension was examined against 128 strains of Gram-negative bacilli. Inhibitory activity was demonstrated against all isolates and bactericidal activity was demonstrated for 68. Sucralfate has inhibitory and bactericidal antibacterial activity which may contribute to its in-vivo clinical efficacy.

New threats to the control of methicillin-resistant Staphylococcus aureus.

Several countries have achieved considerable success in the control of epidemic methicillin-resistant Staphylococcus aureus (MRSA). However, in several hospitals in the UK, MRSA strains of enhanced epidemicity, notably EMRSA-16, are becoming endemic. Our inability to eliminate the cause of a single-strain outbreak is unfamiliar and unnerving. Factors in 'market-led' health care delivery that hinder control of MRSA include a shortage of inpatient beds, patients moving from ward to ward, and more mixed-specialty wards. Increasing use of day treatments leaves an inpatient hospital population with more risk factors for infection. Early discharge of infected patients to convalescent homes, or to homes for the elderly, has created a new reservoir of infected and colonized patients. The emergence of high-level mupirocin resistance may soon also contribute to failure of control. The transfer of vancomycin resistance from Enterococcus faecium to a laboratory strain of S. aureus suggests that, especially in hospitals with both vancomycin-resistant enterococci and MRSA, there is the opportunity for the emergence of vancomycin-resistant MRSA for which there may be no effective antimicrobial prophylaxis or treatment. It is increasingly important to persuade hospital managers that even partial control of MRSA, whilst expensive, is still cost-effective and is a quality issue for individual hospitals. The control of EMRSA-16 in one hospital has recently been estimated to have saved more than 629,000 pounds extra costs. MRSA continues to be at the forefront of those organisms that seriously challenge modern technological medicine and surgery.

Bacterial and fungal infections after liver transplantation: an analysis of 284 patients.

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

Salmonella bacteraemia in sickle cell disease at King's College Hospital: 1976-1991.

A review of all blood culture isolates for the 16 years from 1976 were collated with prospective laboratory and clinical records of 620 sickle cell patients treated at King's College Hospital. Over half of all salmonella bacteraemias diagnosed in the clinical laboratory occurred in sickle cell disease (SCD) patients. Of 21 bacteraemias in SCD patients, 11 (52.3%) were due to Salmonella spp. compared with 23 (0.4%) of 4884 bacteraemias in patients without SCD (P = < 0.00001). In SCD, Gram-negative bacilli were responsible for 16 (76.2%) bacteraemias, of which 11 (68.8%) were due to Salmonella spp. but there were no cases of S. typhi or S. paratyphi. An increase in the number of salmonella infections over the past 5 years were noted in the SCD and non-SCD patients, nine and 16 cases respectively, compared with two and seven cases in the previous decade. However, the recent increase of S. enteritidis phage type 4 in the UK was not evident in SCD patients. These findings have important preventative and therapeutic implications for the management of SCD patients.

Colonial variation in vancomycin resistant Enterococcus faecium.

Vancomycin resistant enterococci are increasingly being isolated from inpatients. This report describes the colonial variation present in most isolates of vancomycin resistant Enterococcus faecium obtained at this hospital. Colonial variants within the same culture were indistinguishable by antimicrobial susceptibility, biochemical reactions, and ribotyping. Failure to appreciate this colonial variation will lead to pure cultures being regarded as contaminated or mixed.

An open, comparative trial of aztreonam with vancomycin and gentamicin with piperacillin in patients with fulminant hepatic failure.

Fifty patients admitted with fulminant hepatic failure and clinically suspected infection were allocated to receive either aztreonam and vancomycin or piperacillin and gentamicin as first line treatment. Fourteen patients died within 48 h of admission and were excluded from the analysis. Of the remaining 36 patients, 16 received aztreonam/vancomycin and 20 piperacillin/gentamicin. There were 18 episodes of infection in the aztreonam/vancomycin group and 24 in the piperacillin/gentamicin group (P = not significant). The most frequent bacterial pathogen was Staphylococcus aureus. Fungal infection developed in 13 patients (nine in the aztreonam/vancomycin group and four in the piperacillin/gentamicin group; P = not significant). Death attributed to infection occurred in 4 (25%) of 16 patients receiving aztreonam/vancomycin and 4 (20%) of 20 receiving piperacillin/gentamicin (P = not significant). Thirteen patients (three in the aztreonam/vancomycin group and ten in the piperacillin/gentamicin group) had clinical and microbiological improvement without addition or substitution of other antibiotics. No side-effects attributed to the study drugs were recorded.

Minimal dose requirements for nasal mupirocin and its role in the control of epidemic MRSA.

Staphylococci are still a leading cause of hospital infection. The success of nasal mupirocin for the control of epidemic methicillin-resistant Staphylococcus aureus (EMRSA), the prevention of colonization of central venous cannulae, and the prevention of septicaemia in haemodialysis patients should encourage the use of minimal dose regimens to minimize the emergence of mupirocin resistance. Mupirocin applied to the anterior nares 4-times daily usually eliminates S. aureus, including EMRSA, within 48 h. Elimination is sustained for several weeks in patients and staff. We recently found that a single dose, or a regimen of 4-times daily for 2 days, eliminated nasal carriage of S. aureus within 24 h; 7 days after a single dose, 92% of the subjects were still cleared; 7 days after the 2-day course, 96% remained free of nasal S. aureus. Ward personnel who are nasal carriers of EMRSA can, provided that other carriage sites are negative, return to work after 2 days of a 4-times daily intranasal regimen. The UK guidelines, recently published in this Journal, recommend an aggressive approach to identifying and eliminating EMRSA, including the elimination of nasal carriage. This approach is increasingly associated with the control of EMRSA in the UK and elsewhere.