Micafungin for the treatment of invasive aspergillosis.

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with neutropenia and those undergoing bone marrow or stem cell transplants. Micafungin is an echinocandin antifungal drug with activity against all major Candida spp. Currently, micafungin is indicated for treatment of invasive candidiasis, oesophageal candidiasis and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia. Micafungin demonstrates in vitro and in vivo activity against Aspergillus spp. It is currently not licensed to treat Aspergillus infections in the UK or USA. This review summarises the current evidence base surrounding the clinical use of micafungin in the treatment of invasive aspergillosis to consider the potential role of micafungin in these patients. There are currently no randomised studies comparing micafungin with standard antifungal therapy. Prospective non-randomised clinical studies, predominantly performed in Japan, involving 492 patients with aspergillosis and 455 febrile patients with chemotherapy-induced neutropenia suggest that micafungin may be as effective as comparator antifungal agents. Other clinical evidence is limited to case reports. Further experience in the form of randomised controlled trials is required to establish the exact role of micafungin in the context of currently available broad-spectrum antifungal agents.

Posaconazole for the treatment of mucormycosis.

Posaconazole (PCZ) is an orally administered, extended-spectrum triazole antifungal agent with activity against the Mucorales. This article describes the clinical and laboratory data supporting its use against this rare group of pathogens. To date, PCZ has been mostly used for salvage therapy and at present there is no strong published clinical evidence to support its role as a single agent in the treatment of mucormycosis. Further studies are required to explore its role as a single agent and in combination therapy for the management of these infections.

Investigation and management of an outbreak of multidrug-carbapenem-resistant Acinetobacter baumannii in Cambridge, UK.

Multidrug-resistant Acinetobacter baumannii resistant to carbapenems (MRAB-C) has become endemic in many hospitals in the UK. We describe an outbreak of MRAB-C that occurred on two intensive care units using ORION criteria (Outbreak Reports and Intervention studies Of Nosocomial infection). All patients colonised or infected with MRAB-C were included. Enhanced infection control precautions were introduced in Phase 1 of the outbreak. The adult neurosciences critical care unit (NCCU) was partially closed in Phase 2 and strict patient segregation, barrier nursing and screening thrice weekly was introduced. When control was achieved, NCCU was reopened (Phase 3) with post-discharge steam cleaning and monthly cleaning of extract and supply vents. There were 19 cases, 16 on NCCU and three on the general intensive care unit (ICU). Mean age was 52 years, with six cases being female. All patients were mechanically ventilated and ten had either an extraventricular drain or intracranial pressure monitoring device in place. Four patients developed a bacteraemia, with one further case of ventriculitis. Nine patients had no clinical evidence of infection and four were identified initially on screening. Ten patients were treated; there were eight deaths. Environmental samples showed heavy contamination throughout NCCU. MRAB-C affects critically ill patients and is associated with high mortality. This outbreak was controlled by early involvement of management, patient segregation, screening of patients and the environment, and increased hand hygiene environmental cleaning and clinical vigilance. A multidisciplinary approach to outbreak control is mandatory.

Occupational injury in a fishmonger with a macular rash, hepatosplenomegaly and pancytopenia.

A 47-year-old fishmonger presented with a history of weight loss and lethargy. On investigation he was found to have myeloma. He presented again before follow up, with a 3-day history of fever and a maculopapular rash. He was admitted to the haematology ward and treated with broad-spectrum antibiotics. Blood cultures were found to be positive for Erysipelothrix rhusiopathiae. Penicillin treatment was given, and he made a good recovery. The importance of occupational illness in an already immunocompromised patient and of taking a proper social and occupational history from patients on admission is illustrated through this case.

Cytomegalovirus infection in immunocompetent patients.

Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are not well documented. From December 1998 through June 2001, serum samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom, were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to confirm CMV infection. A total of 124 patients (106 patients treated by general practitioners [GPs] and 18 hospitalized patients) with CMV infection were identified. The most frequent symptoms were malaise (67%), fever (46%), and sweats (46%), and the most frequent finding was abnormal liver function test results (69%). Twelve percent of patients had a relapsing illness, and many had symptoms that lasted for up to 32 weeks (mean duration of symptoms, 7.8 weeks). GPs reported that there was a significant benefit in making the diagnosis of CMV infection; it provided reassurance and avoided the need for further investigations. We have identified symptoms associated with CMV infection in immunocompetent patients who present to GPs or who are admitted to the hospital.

An antibiotic policy associated with reduced risk of Clostridium difficile-associated diarrhoea.

BACKGROUND: antibiotic-associated diarrhoea caused by Clostridium difficile is increasing in hospitals, and older people are at particular risk. OBJECTIVE: to establish whether reducing patient exposure to injectable third-generation cephalosporins by substituting alternative antibiotics can produce a cost-effective reduction in the incidence of antibiotic-associated diarrhoea. DESIGN: we prospectively investigated 2157 patients admitted to the department of elderly medicine in the year before introduction of antibiotic restrictions and 2037 patients admitted in the following year. Patients admitted to other wards, where antibiotic prescribing was unchanged, acted as controls. SETTING: a 900-bed teaching hospital in Cambridge, UK. MEASUREMENTS: use and cost of injectable antibiotics prescribed in the department of elderly medicine and the other wards studied; occurrence of C. difficile-associated diarrhoea. RESULTS: in the wards for older people, consumption of injectable cephalosporins fell by 92% (compared with 8% on other wards) and cases of C. difficile-associated diarrhoea fell from 98 to 45 (cases in other wards rose from 213 to 253; P < 0.001). The Pound Sterling 8062 increase in injectable antibiotic costs on the elderly wards were offset by the release of 1087 wasted bed-days attributable to the 53 fewer cases, with potential savings of Pound Sterling 212,000. CONCLUSIONS: restricting the consumption of injectable third-generation cephalosporins is a cost-effective method of reducing the incidence of C. difficile-associated diarrhoea.

A pseudo-outbreak of respiratory infection with Acinetobacter species.

We describe an apparent outbreak of respiratory infection with Acinetobacter species involving 14 patients over 8 days. Epidemiological investigation revealed two consecutive pseudo-outbreaks of infection caused by two consecutive, unrelated laboratory errors in the processing of sputum, nasopharyngeal, and endotracheal aspirates.

Role of paraventricular and dorsomedial nuclei of the hypothalamus and central nucleus of the amygdala on muscimol-induced cardiovascular responses.

Gamma-aminobutyric acid (GABA) plays an important role in the central control of cardiovascular functions. Previous evidence indicates that a tonically active GABAergic system exists in forebrain structures. The purpose of this study was to examine the role of the unilateral lesion of the central nucleus of amygdala, paraventricular or dorsomedial nuclei of the hypothalamus on muscimol-induced cardiovascular responses. Electrolytic ablation of nuclei was made by a monopolar isolated electrode under a stereotaxic instrument, 3-5 days before the experiments. Effects of intracerebroventricular injections of muscimol were investigated in intact, lesioned and sham-lesioned rats. On the day of the experiments, blood pressure and heart rate recordings were carried out in male Sprague-Dawley conscious rats. Muscimol produced decreases in arterial blood pressure and heart rate. The hypotensive effect of muscimol was completely inhibited in rats with dorsomedial nucleus lesions, whereas the bradycardic effect was partially prevented. The results indicate that the dorsomedial nucleus of the hypothalamus plays an important role on muscimol-induced blood pressure and heart rate responses.