In order to obtain pan-European data on methicillin-resistant Staphylococcus aureus (MRSA), 43 laboratories from ten European countries each screened 200 consecutive Staphylococcus aureus isolates for methicillin resistance. Only one isolate per patient was permitted. All participants used a uniform oxacillin-supplemented screening plate. MRSA isolates were sent to Munich for reconfirmation and further susceptibility testing. Phage typing of the MRSA strains was performed in Denmark. Of the 7,333 Staphylococcus aureus strains screened, 936 (12.8%) were methicillin resistant. The proportion of MRSA in the various European countries ranged from < 1% in Scandinavia to > 30% in Spain, France and Italy. Rates of resistance to the non-glycopeptide antibiotics were lowest for rifampin and highest for ciprofloxacin. Sixty percent of the methicillin-resistant strains originated from patients in surgical and medical departments, with wounds being the most common isolation source. MRSA was found more frequently in intensive care patients. Only 13% of the strains were non-typable, and 76% of the isolates belonged to phage group III. For each area phage typing detected one or a few dominating (epidemic) types, but 46% of the strains did not belong to these types; the MRSA population is thus a mixture of epidemic and non-epidemic strains. MRSA seems to be a growing problem, especially in southern Europe, where incidence and rates of antibiotic resistance are alarmingly high.

Summary.Invasive aspergillosis is an increasing problem in patients with acute leukaemia, bone marrow transplantation, immunosuppression after solid organ transplantation, or acquired immunodeficiency syndrome. Despite available antifungal treatment, the mortality approaches 100% in patients with dissemination of the infection into the central nervous system (CNS). Using a novel triazole, voriconazole, we successfully treated an Aspergillus brain abscess in a patient with acute leukaemia. Drug levels above the minimal fungicidal concentration for Aspergillus species were detected in cerebrospinal fluid (CSF) specimens, and the treatment achieved an objective response.Keywords: Aspergillus, azoles, brain abscess, immunosuppression, voriconazole.Invasive aspergillosis causes considerable morbidity and mortality in growing numbers of patients treated with intensive chemotherapy, immunosuppressive therapy after solid organ or bone marrow transplantation, or those with acquired immunodeficiency syndrome (Denning & Stevens, 1990). Mortality approaches 100% after dissemination of aspergilli into the central nervous system (CNS), and there have been very few reports of patients surviving this condition (Coleman et al, 1995).A novel triazole, voriconazole, exhibits in vitro activity against various fungi, including Aspergillus species, and has been successfully used in immunocompromised patients with invasive aspergillosis (Denning et al, 1995). We treated a patient with refractory acute leukaemia and an Aspergillus brain abscess with voriconazole after conventional amphotericin B, liposomal amphotericin B and itraconazole had failed. CASE REPORTIn June 1994 an 18-year-old male with acute lymphoblastic leukaemia was admitted for standard induction polychemotherapy (day 1). Because of resistant leukaemia after 9 weeks, he was switched to a more intensive protocol including cytarabine and mitoxantrone (day 63). Fever, despite broad-spectrum antibiotics on day 81, sudden onset of pleural chest pain and a pulmonary infiltrate prompted antifungal treatment with intravenous (i.v.) amphotericin B (Bristol-Myers Squibb, Munich, Germany), which was rapidly escalated to 1·1 mg/kg/d. Because of renal toxicity, antifungal treatment was changed on day 86 to liposomal amphotericin B (AmBisome, Vestar, Braunschweig, Germany) at a maximum dosage of 2·1 mg/kg/d. Meningism developed on day 92 when the cerebrospinal fluid (CSF) contained 1056 cells/ml (96% neutrophils, 2% lymphocytes, 2% monocytes) with negative cultures for bacteria and fungi. A magnetic resonance scan (MR) on day 93 disclosed a hypointense paraventricular lesion suggestive of a fungal brain abscess on T1-weighted images. Defervescence occurred with recovery from neutropenia on day 101, and antifungal therapy was continued with itraconazole (Sempera, Janssen, Neuss, Germany) at a dose of 200 mg three times daily, starting the same day. Progression of the paraventricular lesion and an additional lesion in the cerebellum were documented by a follow-up MR on day 111. Broncho...

The in vitro activities of sitafloxacin, ciprofloxacin, trovafloxacin, levofloxacin, clinafloxacin, gatifloxacin, and moxifloxacin against 5,046 gram-negative bacteria, 3,344 gram-positive cocci, and 406 anaerobes were determined. Sitafloxacin was the most active agent against gram-positive cocci and anaerobes. Against Enterobacteriaceae and nonfermenters, its activity was either equivalent to or better than that of clinafloxacin.Sitafloxacin (DU-6859a) is a new fluoroquinolone active against gram-positive and gram-negative bacteria, including anaerobes (3,7,13). In the present study, the in vitro activities of sitafloxacin against a large number of contemporary and clinically relevant bacterial isolates were determined and compared with those of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin.A total of 8,796 bacterial strains were tested which had been isolated between April 1997 and February 1999 from patients in 24 university hospitals in 14 European countries, 1 in Israel, and 3 in South Africa. Only one isolate per patient was permitted. Strains were reidentified in our laboratory using a combination of standard methods and either the VITEK or the API system (BioMerieux, s'Hertogenbosch, The Netherlands). MICs were determined by a microdilution method described by the National Committee for Clinical Laboratory Standards (15), using cation-adjusted Mueller-Hinton broth. For testing Streptococcus spp. and Neisseria spp., 5% lysed horse blood was added. Haemophilus spp. were tested using Haemophilus test medium. The inoculum was adjusted to 5 ϫ 10 5 CFU/ml. Plates were read after 20 to 24 h of incubation at 35°C in ambient air. Anaerobic bacteria were tested with WilkinsChalgren broth and a final inoculum of 10 6 CFU/ml. Plates were read after 48 h of incubation at 35°C in an anaerobic environment (16).The results of susceptibility testing are presented as the MICs at which 50 and 90% of the isolates tested are inhibited (MIC 50 and MIC 90 ) and the ranges of MICs (Table 1). Sitafloxacin was very active against enterobacterial species, inhibiting 96.9% of the 3,129 strains at a concentration of 1 g/ml. The MIC 50 s ranged from Յ0.008 to 1 g/ml, and the MIC 90 s ranged from 0.015 to 2 g/ml. The MIC 90 for Providencia spp. was the highest (2 g/ml), followed by those for Enterobacter aerogenes and Escherichia coli (1 g/ml for each). These three species also exhibited the highest rates of ciprofloxacin resistance (51.6, 38.5, and 14.6%, respectively). The MIC 90 s of sitafloxacin for Citrobacter koseri, Klebsiella oxytoca, Pantoea agglomerans, Proteus vulgaris, salmonellae, Serratia liquefaciens, Shigella spp., and Yersinia enterocolitica ranged from 0.015 to 0.12 g/ml and were similar to those of ciprofloxacin. However, sitafloxacin was four times more active than ciprofloxacin against Citrobacter freundii, Klebsiella pneumoniae, Morganella morganii, and Serratia marcescens and at least eight times more active against E. aerogenes, Enterobacter cloacae, E. coli, and Prot...

The frequency of development of resistance during antibiotic therapy was evaluated by reviewing the literature according to prescribed criteria. Mean resistance rates were calculated to be 9.2% for broad spectrum penicillins, 8.6% for second and third generation cephalosporins, 10.0% for latamoxef, 4.7% for imipenem, 11.8% for ciprofloxacin and 13.4% for aminoglycosides. Emergence of resistance of the infecting organism was associated with therapeutic failure in about half of the cases with the exception of patients treated with aminoglycosides in whom development of resistance resulted in treatment failure in 85% of the cases. The possible benefit of combination therapy in terms of resistance development is discussed.