A critical view on the current use of daptomycin in Spain: The daptomise study.

BACKGROUND: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing. METHODS: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. RESULTS: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%. CONCLUSION: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases.

Nocardiosis at the turn of the century.

Nocardia species is an uncommon pathogen that affects both immunosuppressed and immunocompetent patients. The clinical and microbiologic spectrum of nocardiosis has changed recently due to the widespread use of cotrimoxazole prophylaxis, the emergence of new types of immunosuppressed patients, and the improved identification of isolates using molecular techniques. Nocardia asteroides was traditionally considered the predominant organism, and prophylaxis with cotrimoxazole was considered almost universally protective. We conducted the current study to determine the incidence of nocardiosis and its microbiologic and clinical characteristics in a general hospital over the last 12 years. We reviewed the clinical records of all patients in whom Nocardia species was isolated from clinical specimens between 1995 and 2006. Nocardia isolates were identified by standard procedures and by 5' end 16S rRNA gene polymerase chain reaction (PCR) and sequencing. Susceptibility to cotrimoxazole, minocycline, imipenem, linezolid, and amikacin was determined by the broth microdilution method following the guidelines of the Clinical and Laboratory Standards Institute.The incidence of Nocardia infections did not increase significantly during the study period (0.39/100,000 inhabitants in 1995-1998 and 0.55/100,000 inhabitants in 2003-2006). Nocardia was recovered from 43 patients. Six were considered to be colonized. The colonizing species were N. farcinica, N. nova, and N. asteroides. All colonized patients had severe underlying pulmonary conditions and were treated with antimicrobials (6 patients) or corticosteroids (4 patients). Invasive nocardiosis was diagnosed in 37 patients (86.5% were men, and their mean age was 55.8 +/- 17.3 yr). The most common underlying condition in our institution was human immunodeficiency virus (HIV) infection (10 patients; 27%), followed by chronic obstructive pulmonary disease (8 patients; 21.6%), autoimmune diseases (8 patients; 21.6%), solid organ transplantation (7 patients; 18.9%), and cancer (4 patients; 10.8%). The most important risk factor for nocardiosis was corticosteroid administration (23 patients; 62.2%). Nocardiosis affected the lungs in 26 cases (70.3%), the skin in 3 cases (8.1%), and the central nervous system in 2 cases (5.4%). It was disseminated in 5 cases (13.5%) and caused otomastoiditis in 1 (2.7%). The species identified were N. cyriacigeorgica (32.4%), N. farcinica (24.3%), N. otitidiscaviarum (10.8%), N. veterana (8.1%), N. nova (5.4%), N. abscessus (5.4%), N. asiatica (2.7%), N. beijingensis (2.7%), N. brasiliensis (2.7%), N. carnea (2.7%), and Nocardia species (2.7%).Linezolid and amikacin were uniformly active against all the isolates, whereas 29.7% of isolates showed intermediate susceptibility to minocycline (minimum inhibitory concentration = 2 mg/L), 10.8% were resistant to cotrimoxazole, and 5.4% were resistant to imipenem. Nocardiosis occurred while the patients were on cotrimoxazole prophylaxis in 8 cases (21.6%). The strains isolated from these patients were susceptible to cotrimoxazole in 5 cases (62.5%) and resistant in 3 (37.5%). Overall, 13 patients died (35.1%); related mortality was 21.6% (8 patients). We conclude that HIV infection has become the most common underlying condition for invasive nocardiosis in our institution, followed by chronic lung disease. Previous use of corticosteroids was the main risk factor and was present in more than half the patients. New species of Nocardia have been identified, and administration of cotrimoxazole prophylaxis should no longer be considered highly reliable protection against nocardiosis. Larger studies of nocardiosis are required to better identify risk factors associated with mortality, and alternative and more effective methods of prevention must be developed.