Cerebral Nocardiosis: A Rare Cause of Hemiplegia in the Acute Medicine Unit.

Nocardiosis, a rare infection occurring mostly in immunosuppressed patients can present with neurological complications including cerebral abscess formation, and is associated with high morbidity and mortality. We describe the case of a 54-year-old immunocompetent man with cerebral nocardiosis, who presented with sudden onset hemiparesis in an acute medicine unit. He required three craniotomies with excision, following failure to respond to antimicrobial therapy, with subsequent clinical improvement and radiological resolution of multiple cerebral abscesses. Challenges in diagnosis and management of hemiparesis in the acute medical unit are discussed. Successful management of cerebral nocardiosis require early communication with a neurosurgical unit, neuropathology and microbiology services to optimise management with targeted antimicrobial therapy.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Immunovirological correlates in human rabies treated with therapeutic coma.

A 37-year-old woman was admitted to hospital and over the next 5 days developed a progressive encephalitis. Nuchal skin biopsy, analyzed using a Rabies TaqMan(c) PCR, demonstrated rabies virus RNA. She had a history in keeping with exposure to rabies whilst in South Africa, but had not received pre- or post-exposure prophylaxis. She was treated with a therapeutic coma according to the "Milwaukee protocol," which failed to prevent the death of the patient. Rabies virus was isolated from CSF and saliva, and rabies antibody was demonstrated in serum (from day 11 onwards) and cerebrospinal fluid (day 13 onwards). She died on day-35 of hospitalization. Autopsy specimens demonstrated the presence of rabies antigen, viral RNA, and viable rabies virus in the central nervous system.

A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults.

BACKGROUND: Invasive Candida infection among nonneutropenic, critically ill adults is a clinical problem that has received increasing attention in recent years. Poor performance of extant diagnostic modalities has promoted risk-based, preemptive prescribing in view of the poor outcomes associated with inadequate or delayed antifungal therapy; this risks unnecessary overtreatment. A rapid, reliable diagnostic test could have a substantial impact on therapeutic practice in this patient population. METHODS: Three TaqMan-based real-time polymerase chain reaction assays were developed that are capable of detecting the main medically important Candida species, categorized according to the likelihood of fluconazole susceptibility. Assay 1 detected Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida dubliniensis. Assays 2 and 3 detected Candida glabrata and Candida krusei, respectively. The clinical performance of these assays, applied to serum, was evaluated in a prospective trial of nonneutropenic adults in a single intensive care unit. RESULTS: In all, 527 specimens were obtained from 157 participants. All 3 assays were run in parallel for each specimen; they could be completed within 1 working day. Of these, 23 specimens were obtained from 23 participants categorized as having proven Candida infection at the time of sampling. If a single episode of Candida famata candidemia was excluded, the estimated clinical sensitivity, specificity, and positive and negative predictive values of the assays in this trial were 90.9%, 100%, 100% and 99.8%, respectively. CONCLUSIONS: These data suggest that the described assays perform well in this population for enhancing the diagnosis of candidemia. The extent to which they may affect clinical outcomes, prescribing practice, and cost-effectiveness of care remains to be ascertained.

Spondylodiscitis due to Aerococcus viridans.

Aerococcus viridans is a microaerophilic, Gram-positive, catalase-negative coccus, found singly or in tetrads. To date, no case of spondylodiscitis due to this organism has been reported. We report what we believe to be the first case of spondylodiscitis caused by A. viridans, in a patient with decompensated liver failure, and discuss the possible pathogenesis of this rather uncommon pathogen in this case.

Comparison of serum and whole-blood specimens for the detection of Candida DNA in critically ill, non-neutropenic patients.

In contrast to the multitude of studies on fungal PCR assay methods, little work has been reported evaluating Candida PCR performance when using whole blood compared with serum in candidaemic patients. Here, a comparison of the performance of whole-blood and serum specimens using a set of real-time PCR Candida species assays is described. Specimens were collected prospectively from non-neutropenic adults who were recruited to a diagnostic clinical trial, the primary purpose of which was to verify the performance of the assays using serum; in all, 104 participants also had whole-blood specimens submitted for analysis in addition to the serum specimen. Of these participants, 10 had laboratory-confirmed candidaemia and 94 were categorized as being 'unlikely' to have invasive Candida infection. PCR results from the whole-blood specimens are presented here and compared with the results from serum specimens in this subgroup among whom both specimen types were obtained contemporaneously. All participants with candidaemia were PCR-positive from serum samples; however, only seven were PCR-positive from whole blood. All specimens from patients in the 'unlikely' category were PCR-negative in both types of specimen. Moreover, DNA extraction from serum required 1 h; extraction from whole blood required approximately 3 h. These data tentatively suggest that, overall, serum is an appropriate specimen for Candida PCR for detection of candidaemia in non-neutropenic adults.

Improving molecular detection of Candida DNA in whole blood: comparison of seven fungal DNA extraction protocols using real-time PCR.

The limitations of classical diagnostic methods for invasive Candida infections have led to the development of molecular techniques such as real-time PCR to improve diagnosis. However, the detection of low titres of Candida DNA in blood from patients with candidaemia requires the use of extraction methods that efficiently lyse yeast cells and recover small amounts of DNA suitable for amplification. In this study, a Candida-specific real-time PCR assay was used to detect Candida albicans DNA in inoculated whole blood specimens extracted using seven different extraction protocols. The yield and quality of total nucleic acids were estimated using UV absorbance, and specific recovery of C. albicans genomic DNA was estimated quantitatively in comparison with a reference (Qiagen kit/lyticase) method currently in use in our laboratory. The extraction protocols were also compared with respect to sensitivity, cost and time required for completion. The TaqMan PCR assay used to amplify the DNA extracts achieved high levels of specificity, sensitivity and reproducibility. Of the seven extraction protocols evaluated, only the MasterPure yeast DNA extraction reagent kit gave significantly higher total nucleic acid yields than the reference method, although nucleic acid purity was highest using either the reference or YeaStar genomic DNA kit methods. More importantly, the YeaStar method enabled C. albicans DNA to be detected with highest sensitivity over the entire range of copy numbers evaluated, and appears to be an optimal method for extracting Candida DNA from whole blood.

Rapid differentiation between fluconazole-sensitive and -resistant species of Candida directly from positive blood-culture bottles by real-time PCR.

In view of both the delay in obtaining identification by conventional methods following blood-culture positivity in patients with candidaemia and the close relationship between species and fluconazole (FLC) susceptibility, early speciation of positive blood cultures has the potential to influence therapeutic decisions. The aim was to develop a rapid test to differentiate FLC-resistant from FLC-sensitive Candida species. Three TaqMan-based real-time PCR assays were developed to identify up to six Candida species directly from BacT/Alert blood-culture bottles that showed yeast cells on Gram staining at the time of initial positivity. Target sequences in the rRNA gene complex were amplified, using a consensus two-step PCR protocol, to identify Candida albicans, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, Candida glabrata and Candida krusei; these are the most commonly encountered Candida species in blood cultures. The first four of these (the characteristically FLC-sensitive group) were identified in a single reaction tube using one fluorescent TaqMan probe targeting 18S rRNA sequences conserved in the four species. The FLC-resistant species C. krusei and C. glabrata were detected in two further reactions, each with species-specific probes. This method was validated with clinical specimens (blood cultures) positive for yeast (n=33 sets) and the results were 100 % concordant with those of phenotypic identification carried out concomitantly. The reported assay significantly reduces the time required to identify the presence of C. glabrata and C. krusei in comparison with a conventional phenotypic method, from approximately 72 to <3 h, and consequently allows optimization of the antifungal regimen at an earlier stage.

Frequency and distribution of group I intron genotypes of Candida albicans colonising critically ill patients.

A study is performed to examine the distribution and frequency of 25S rRNA intron genotypes of Candida albicans isolated from different anatomical sites of patients in an intensive care unit (ICU) setting. Germ-tube positive Candida isolates (n=65) from 65 patients are included and isolates are characterised by 25S intron genotyping, whereby all can be subdivided into four genotypes (A-D). Results demonstrated that there were no significant differences between the frequency and genotype distribution of the Candida isolates and the anatomical site of colonisation. Furthermore, analysis of the transposable intron region in the 25S rRNA gene demonstrated equal distribution, regardless of age and anatomical site of isolation (groin, throat, etc.). Therefore, there does not appear to be any selective pressure associated with any anatomical site, resulting in an ecological shift in the frequency of genotypes present. This suggests that C. albicans intron genotypes equally colonise those sites of the body examined in this study. Although such an ecological finding as this is interesting, it perpetuates the continued need to find a genotypic typing scheme that helps to identify the source (nosocomial or endogenous) and mode of entry of C. albicans into patients in the ICU setting, resulting in C. albicans bloodstream infection.

Pathogenic organisms associated with artificial fingernails worn by healthcare workers.

OBJECTIVE: To determine differences in the identity and quantity of microbial flora from healthcare workers (HCWs) wearing artificial nails compared with control HCWs with native nails. DESIGN: Two separate studies were undertaken. In study 1, 12 HCWs who did not normally wear artificial nails wore polished artificial nails on their nondominant hand for 15 days. Identity and quantity of microflora were compared between the artificial nails and the polished native nails of the other hand. In study 2, the microbial flora of the nails of 30 HCWs who wore permanent acrylic artificial nails were compared with that of control HCWs who had native nails. In both studies, nail surfaces were swabbed and subungual debris was collected to obtain material for culture. Staphylococcus aureus, gram-negative bacilli, enterococci, and yeasts were considered to be potential pathogens. All organisms were identified and quantified. RESULTS: In study 1, potential pathogens were isolated from more samples obtained from artificial nails than native nails (92% vs. 62%; P<.001). Colonization of artificial nails increased over time; by day 15, 71% of cultures yielded a pathogen compared with 21% on day 1 (P=.004). A significantly greater quantity of organisms (expressed as mean log10 colony-forming units +/- standard deviation) was isolated from the subungual area than the nail surface; this was noted for both artificial (5.0+/-1.4 vs. 4.1+/-1.0; P<.001) and native nails (4.9+/-1.3 vs. 3.7+/-0.8; P<.001). More organisms were found on the surface of artificial nails than native nails (P=.008), but there were no differences noted in the quantities of organisms isolated from the subungual areas. In study 2, HCWs wearing artificial nails were more likely to have a pathogen isolated than controls (87% vs. 43%; P=.001). More HCWs with artificial nails had gram-negative bacilli (47% vs. 17%; P=.03) and yeasts (50% vs. 13%; P=.006) than control HCWs. However, the quantities of organisms isolated from HCWs wearing artificial nails and controls did not differ. CONCLUSIONS: Artificial fingernails were more likely to harbor pathogens, especially gram-negative bacilli and yeasts, than native nails. The longer artificial nails were worn, the more likely that a pathogen was isolated. Current recommendations restricting artificial fingernails in certain healthcare settings appear justified.

Colonization with vancomycin-resistant Enterococcus faecium: comparison of a long-term-care unit with an acute-care hospital.

OBJECTIVE: To compare the epidemiology of vancomycin-resistant Enterococcus faecium (VRE) in a long-term-care unit and an acute-care hospital. DESIGN: Point-prevalence surveys for VRE rectal colonization of patients were carried out over a 21-month period in patients in a long-term-care unit and an acute-care hospital (medical ward and intensive-care units). The environment and hands of healthcare workers also were sampled for VRE. Contour-clamped homogeneous electric field (CHEF) electrophoresis was used to evaluate possible transmission among roommates and the relatedness of patient strains to those in the environment and on the hands of healthcare workers. SETTING: A 200-bed Veterans Affairs Medical Center with an attached 90-bed long-term-care unit. RESULTS: From December 1994 to January 1996, rectal VRE colonization of patients in the long-term-care unit increased significantly from 9% to 22%. In contrast, patients on the medical ward rarely were colonized after the first survey in December 1994, and only two intensive-care-unit patients were found to be colonized during the four surveys. The environment was contaminated persistently in the long-term-care unit. In the four surveys, carriage of VRE on hands of healthcare workers varied from 13% to 41%; 65% of healthcare workers with VRE found on their hands worked in the long-term-care unit. Seven different strains were identified by CHEF typing. Although the initial survey found only vanA strains, subsequent surveys showed vanB strains also were present. CONCLUSIONS: Residents of a long-term-care unit frequently were colonized with VRE, but infections were uncommon in this population. The environment of the long-term-care unit was contaminated with VRE, and VRE was found frequently on the hands of healthcare workers in this unit. Both vanA and vanB genotypes were found in this setting.

Risk factors for colonization with yeast species in a Veterans Affairs long-term care facility.

OBJECTIVES: To assess colonization and serious infection with yeasts and the risk factors that are associated with colonization by these organisms. DESIGN: Monthly surveillance for colonization and infection over a period of 2 years. SETTING: A long-term-care facility (LTCF) attached to an acute-care Veterans Affairs Medical Center. PARTICIPANTS: The 543 men and 10 women in the facility. MEASUREMENTS: Colonization and serious infection rates with yeasts. Analysis of risk factors associated with yeast colonization of residents. RESULTS: Colonization rates were relatively stable during the 2-year period (53+/-1.8% patients colonized per month). Candida albicans was the most common colonizer, found in 35+/-.9% of patients colonized per month. The pharynx was the most commonly colonized site, with 41+/-1.4% of patients per month with pharyngeal colonization. Eighty-four percent of patients remaining in the facility for 3 or more months were colonized by yeast at some time during their stay. Presence of neurogenic bladder, leg amputation, or a low serum albumin were independently associated with yeast colonization; neither diabetes mellitus nor functional status was a risk factor for colonization by yeasts. Only four serious yeast infections in four patients (esophagitis and three urinary tract infections) were found during the 2-year period; all infections occurred in patients who were colonized by yeasts previously. CONCLUSION: In our LTCF, colonization of patients by yeasts occurred commonly in those residents remaining in the facility for 3 or more months. However, serious yeast infections occurred infrequently. It is likely that colonization of residents of LTCFs by yeasts may only become clinically important when the patient is transferred to an acute-care hospital where additional risk factors may allow the development of serious yeast infection.

Comparison of API20C with molecular identification of Candida spp isolated from bloodstream infections.

A study was carried out to compare the API20C technology with polymerase chain reaction amplification and direct sequencing of the short internal transcribed spacer region 2 (ITS2) for the identification of 58 isolates of invasive candida species obtained from patients with bloodstream infections over the seven year period 1994 to 2000. Overall, there was only one disagreement between the phenotypic and genotypic identification, where the API scheme identified the isolate as C albicans but the molecular method identified it as C dubliniensis. This study demonstrated that the API20C method is useful in the identification of Candida spp isolated from blood culture and that molecular methods do not enhance identifications made using the API20C scheme. However, for correct reporting of C dubliniensis, an emerging bloodborne pathogen, it is recommended that all isolates identified as C albicans by the API20C scheme are further examined phenotypically and/or genotypically.

Mycobacterium avium complex endocarditis: spurious diagnosis resulting from laboratory cross contamination.

Contamination between specimens within clinical microbiology laboratories may be responsible for spurious outbreaks of mycobacterial infections. We report the case of a patient who had culture-negative endocarditis and whose cardiac tissue obtained at surgery yielded Mycobacterium avium complex (MAC). Epidemiologic investigation suggested cross contamination probably occurred during processing of the sputum specimens of a patient with pulmonary MAC disease and the cardiac samples from our patient; molecular strain typing showed the isolates from both patients to be identical. When mycobacterial infection rates increase or an unexpected case of mycobacterial infection occurs, the clinician should be alert to the possibility of cross contamination in the laboratory as a possible explanation.

Catheter-related bloodstream infection in adult haematology patients: catheter removal practice and outcome.

The aim of the present study was to describe the practice of central venous catheter (CVC) removal and outcomes of catheter-related bloodstream infection (CR-BSI) in adult haematology patients. Patients were identified retrospectively according to diagnosis coding of inpatient episodes and evaluated when, on examination of medical records, there had been evidence of sepsis with strong clinical suspicion that the source was the CVC. Demographic and bacteriological data, as well as therapeutic measures and clinical outcomes, were recorded. One hundred and three patient episodes were evaluated. The most frequent type of CVC was the Hickman catheter and the most frequently isolated pathogen was coagulase-negative staphylococci. Twenty-five percent of episodes were managed with catheter removal. Treatment failure, defined as recurrence of infection within 90 days or mortality attributed to sepsis within 30 days, occurred significantly more frequently in the group managed without catheter removal (52.5% versus 4%, P < 0.05). Specifically, 90-day recurrence was more common when the catheter was retained (46% versus 0%). However the difference in 30-day attributable mortality (7% versus 4%) was not significantly different. Notably, no significant difference between the two groups emerged in respect of other measured characteristics that had been considered as potential determinants of outcome. More frequent CVC removal for CR-BSI, in this population, should be considered. Management of CR-BSI without catheter removal is associated with treatment failure, morbidity and carries significant resource implications.

Treatment of systemic fungal infections in older patients: achieving optimal outcomes.

Systemic fungal infections are an increasing problem in older adults. For several of the endemic mycoses, this increase is the result of increased travel and leisure activities in areas endemic for these fungi. Immunosuppressive agents, care in an intensive care unit, and invasive devices all contribute to infection with opportunistic fungi. Treatment of systemic fungal infections is usually with an azole or amphotericin B. The preferred regimen depends on the specific fungal infection, the site and the severity of the infection, the state of immunosuppression of the patient and the possible toxicities of each drug for a specific patient. In older adults, drug-drug interactions between the azoles and drugs commonly prescribed for older persons may lead to serious toxicity, and absorption of itraconazole can be problematic. Amphotericin B is associated with significant nephrotoxicity, especially in older adults with pre-existing renal disease, and infusion-related adverse effects. Newer lipid formulations of amphotericin B can obviate some of these toxicities, but their role in the treatment of systemic fungal infections in older adults has not yet been clarified.

Trends in the epidemiology of Candida bloodstream infections in Northern Ireland between January 1984 and December 2000.

OBJECTIVE: To describe the epidemiology of Candida bloodstream infections (BSI) in Northern Ireland. METHODS: Retrospective collation of data relating to all clinically significant BSI in a university teaching hospital, which had been recorded prospectively, between 1984 and 2000. RESULTS: One hundred and forty five episodes of candidaemia occurred in 144 patients (of mean age 56.6 years). The contribution of Candida spp. towards all significant BSI increased from 2.0% to 2.5%. C. albicans was the most frequently isolated species, however, its incidence fell from 70% to 53% during the study period. The greatest increase in incidence was seen with C. glabrata which was the most common non-albicans species. Twenty-nine per cent of isolates occurred in patients from an intensive care unit and, surprisingly, a further 25.5% occurred in patients from a surgical service. CONCLUSION: There appears to be several subtle differences in the epidemiology of candidal BSI between Northern Ireland and other countries.

Candida parapsilosis: two cases of endocarditis in association with the Toronto stentless porcine valve.

Candida parapsilosis endocarditis in association with prosthetic heart valves is rare. We report the first two cases of C. parapsilosis endocarditis on the Toronto stentless porcine valve (TSPV) and the first reported case of successful elimination of infection without lifelong antifungal therapy.

Genital schistosomiasis.

Schistosomiasis is the most serious helminthic infection in the United Kingdom. Female genital schistosomiasis affects 9-13 million women worldwide, mainly in areas where Schistosoma haematobium is endemic. With increasing tourism to these areas, this diagnosis is being encountered more frequently in the West. We present 2 cases of vulval schistosomiasis that were presented to our department in 1999 and 2000.

Opportunistic fungal infections: filamentous fungi and cryptococcosis.

Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.