Guidelines for the control of glycopeptide-resistant enterococci in hospitals.

The increase since the mid 1980s in glycopeptide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

Antiallergic activity of tetracyclic derivatives of quinoline-2-carboxylic acid. 2. Some benzothienoquinolinecarboxylic acids.

Some benzothienoquinolinecarboxylic acids were synthesized and tested in the rat passive cutaneous anaphylaxis (PCA) assay as potential antiallergic agents. Many of the compounds showed activity comparable to that shown by disodium cromoglycate (DSFG); two of them, 1,4-dihydro-4,6,6-trioxo-5-chloro[1]benzothieno[2,3-g]quinoline-2-carboxylic acid and 1,4-dihydro-1,7-dioxo[1]benzothieno[3,2-f]quinoline-3-carboxylic acid, showed potency approximately eightfold greater than that of DSCG in the PCA assay.

Synthesis and antiallergic activity of some acidic derivatives of 4H-pyrimido[2,1-b]benzazol-4-ones.

Reactions of 2-aminobenzothiazole, 2-aminobenzoxazole, and 2-amino-1-methylbenzimidazole with dimethyl aminofumarate (DMAF) or diethyl ethoxymethylenemalonate (DEEM) led to 2- or 3-carboxy-4H-pyrimido[2,1-b]-benzazol-4-ones, respectively. Subsequent derivatization of these carboxylic acids gave the corresponding tetrazolylcarboxamides and tetrazoles. These acidic compounds were tested in the rat passive cutaneous anaphylaxis (PCA) assay as potential antiallergic agents. Many of the compounds displayed activity comparable to that shown by disodium cromoglycate (DSCG) when tested by the intraperitoneal route, and some, unlike DSCG, also showed activity when tested orally.

Mycobacterium tuberculosis infection in pediatric liver transplant recipients.

OBJECTIVES: To study the incidence, clinical presentation, management, complications and outcome of tuberculosis in pediatric liver transplant recipients. METHODS: A retrospective review of the medical records of children who underwent liver transplantation between 1991 and 1998. RESULTS: Mycobacterium tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were common presentations; one-half had normal chest radiographs. The median time to confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests contributing to diagnosis included: Ziehl-Neelsen (ZN) stain (2 patients), M. tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and histopathology (4 patients). Family health screening was productive for 4 patients. Duration of treatment varied from 9 to 18 months. Isoniazid-induced hepatitis was observed in 2 patients but resolved with dose reduction. Two patients died while receiving treatment, one of Klebsiella spp. septicemia and the other of pulmonary hemorrhage. CONCLUSIONS: Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug-induced hepatotoxicity.

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.

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.

The emergence of Enterococcus faecium resistant to glycopeptides and other standard agents--a preliminary report.

We describe the emergence of vancomycin-resistant (VmR) Enterococcus faecium on a liver unit. Over a 22 month period, 110 patients acquired VmR E. faecium. Ribotyping identified 116 patient isolates. Five ribotypes accounted for 78% of patient isolates, the maximum number of patient isolates of a single ribotype was 37, and five clusters of four ribotypes were found. Seven patients acquired more than one ribotype. Environmental sampling yielded VmR E. faecium of the same ribotype as concurrent patient isolates. Clinical specimens from 38 liver transplant patients yielded VmR E. faecium and these were compared to 29 who acquired vancomycin-sensitive (VmS) E. faecium. Logistic regression analysis indicated that duration of admission was the only independent risk factor for acquisition of VmR E. faecium.

The evaluation of residual antimicrobial activity on hands and its clinical relevance.

A model for evaluation of the residual activity of agents used for hygienic hand disinfection, which relates closely to the "in-use" setting, is described. We looked for residual activity following hand disinfection by a standard method with soap and water and four skin disinfectants in common use. Two test organisms known to have caused cross-infection and having clinically-significant antibiotic resistance were used: a strain of vancomycin-resistant Enterococcus faecium and one of gentamicin-multiply-resistant Enterobacter cloacae. Both organisms survived well on artificially inoculated hands. Residual activity on previously disinfected hands against both test organisms was most marked for alcoholic chlorhexidine ('Hibisol') which showed a 4 log10 reduction within 1 min of inoculation. Chlorhexidine digluconate skin cleanser ('Hibiscrub') and povidone-iodine surgical scrub ('Betadine') also had marked residual activity, but less than alcoholic chlorhexidine. 60% Isopropanol showed no residual activity and, except for marginal activity against E. cloacae, soap and water showed little residual activity. The residual activity of alcoholic chlorhexidine may be useful to control cross-infection with those multiply-resistant strains which survive well on fingers previously washed with soap and water.

Hygienic hand disinfection for the removal of epidemic vancomycin-resistant Enterococcus faecium and gentamicin-resistant Enterobacter cloacae.

An outbreak strain of Enterococcus faecium, bearing plasmid-mediated vancomycin resistance, and an epidemic gentamicin-resistant, multiply-resistant strain of Enterobacter cloacae, both survived well on fingertips of three volunteers for up to 30 minutes after inoculation. Hand disinfection of inoculated fingers with 60% isopropyl alcohol, or with alcoholic chlorhexidine, reliably gave a 4 log10 reduction of both test organisms. Enterobacter cloacae could not be detected in any finger washings, even by enrichment culture. Chlorhexidine digluconate and povidone-iodine were also effective against E. faecium and Ent. cloacae, giving 4 log10 reductions, but finger washings taken after disinfection yielded low counts of the test strains, e.g. less than 45 recoverable colony forming units (cfu) per finger. Handwashing with soap and water was the least reliable method. The epidemicity, serious antimicrobial multiple resistance and survival on finger-tips of these two strains justifies the use of handwashing agents which have maximum effect. The rapid bactericidal (and residual) activity of alcoholic chlorhexidine suggests that, on the basis of present evidence, it is the preferred agent for hygienic hand disinfection against such strains.

Some normal clinical chemistry values for cerebrospinal fluid of the rhesus monkey (Macaca mulatta).

The concentrations of many components of the cerebrospinal fluid are much lower than in serum. Values for sodium, potassium, calcium and magnesium are similar to those in other primates. Activities of alkaline phosphatase (18.7 U/1), creatine phosphokinase (9.9 U/1), glutamine oxaloacetate transaminase (13.7 U/1), glutamine pyruvate transaminase (9.2 U/1), gamma-glutamyl transpeptidase (3.1 U/1), alpha-hydroxybutyrate dehydrogenase (33.0 U/1, lactate dehydrogenase (47.2 U/1) and sorbitol dehydrogenase (3.9 U/1), and levels of zinc (1.0 mu g/dl), copper (2.6 mu g/dl), iron (35.9 mu g/dl) and triglycerides (33.2 mu g/dl) have not previously been reported for this species. Values for free amino acids, total protein, creatinine and urea nitrogen are compared with those of other primates. The use of gradient pore polyacrylamide gel electrophoresis for analysing proteins of CSF is described.

Enterococcus faecium in hospitals.

Most of the characteristics that have ensured the success of enterococci as nosocomial pathogens were described early in this century. Enterococcus faecium and Enterococcus faecalis, the enterococci most frequently isolated from clinical material, differ fundamentally. The intrinsic antimicrobial resistance of Enterococcus faecium, supplemented by acquired resistance mechanisms, can generate a glycopeptide-multiply-resistant nosocomial pathogen that survives on hands and in the environment, and has the potential for intra-hospital and inter-hospital spread. The use of terms such as 'an enterococcus', 'faecal streptococci' and 'group D streptococci' have hindered, and still hinder, our understanding of a species rapidly emerging as the most problematic of nosocomial pathogens.

Survival of Neisseria gonorrhoeae isolates of different auxotypes in six commercial transport systems.

We determined the rates of survival of six clinical and two control strains of Neisseria gonorrhoeae in six commercial transport systems, using NCCLS standard M40-A methodology. Differences in strain recovery and system performance were marked. A strain less robust than the recommended ATCC 43069 would provide a more exacting standard.

Survival of six auxotypes of Neisseria gonorrhoeae in transport media.

The survival in transport media of 30 strains of gonococci was determined. These strains comprised five distinguishable strains of each of six auxotypes. Survival of different auxotypes varied significantly, but this variability was reduced by charcoal. Delayed swab processing could yield isolates unrepresentative of those causing infection in a sampled patient population.

Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group.

An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia.

Infection of foot ulcers with Staphylococcus aureus associated with increased mortality in diabetic patients.

Diabetic patients with foot ulceration have a poorer prognosis than those without ulceration. The reason for this is unclear, but there is considerable interest in the putative links between infection and atherogenesis, and it is notable that diabetic foot ulcers (DFU) are often infected with Staphylococcus aureus and the main cause of death in DFU patients is ischaemic heart disease. We examined the 5 year survival of 71 diabetic patients who presented with foot ulcers that were newly infected (Sa group, n = 56) or not infected at all during the study period (non-Sa group, n = 15) with S. aureus. Twenty-nine patients (52%) infected with S. aureus died compared with three patients (20%) whose foot ulcers were not infected with S. aureus. The patients in the two groups were similar in age and duration of diabetes. The overall five year mortality rate was 10.4% per year for those infected, significantly higher than the average of 4.0% for patients without infection (p = 0.015). None of the patients was bacteraemic or died directly from sepsis. Infection of DFU by S. aureus may increase the risk of death in diabetic patients.

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.

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.