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OBJECTIVES: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available ß-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. METHODS: BDG results by Wako ß-glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. RESULTS: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1-3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut-offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). CONCLUSIONS: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.
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Pruebas Diagnósticas de Rutina/métodos , Infecciones Fúngicas Invasoras/diagnóstico , beta-Glucanos/sangre , Anciano , Antifúngicos/uso terapéutico , Caspofungina/uso terapéutico , Femenino , Fluconazol/uso terapéutico , Humanos , Unidades de Cuidados Intensivos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Límite de Detección , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Voriconazol/uso terapéuticoRESUMEN
Phaeohyphomycosis is a diverse group of uncommon mycotic infections caused by dematiaceous fungi which appears to be increasing in incidence, particularly in transplant recipients. Alternaria is the most frequent isolated genus. Subcutaneous, pulmonary and disseminated disease are the most common sites of Alternaria infection in solid organ transplant recipients. We report the first case, to our knowledge, of a kidney transplant recipient with Alternaria alternata subcutaneous infection who was successfully treated with isavuconazole.
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Antifúngicos/uso terapéutico , Trasplante de Riñón/efectos adversos , Nitrilos/uso terapéutico , Feohifomicosis/tratamiento farmacológico , Piridinas/uso terapéutico , Tejido Subcutáneo/microbiología , Triazoles/uso terapéutico , Anciano , Alternaria/inmunología , Alternaria/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/cirugía , Masculino , Feohifomicosis/diagnóstico , Feohifomicosis/microbiología , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to monitor recent changes in the epidemiology of candidemia and in the antifungal susceptibility profiles of Candida isolates in one Italian region (Lombardy) in 2014-2015 in comparison with two other studies performed in the same area in 1997-1999 and in 2009. METHODS: A laboratory-based surveillance was conducted in 11 microbiology laboratories. Identification of Candida isolates from 868 episodes and antifungal susceptibility testing (YeastOne) was performed locally. RESULTS: A progressive increase in the rate of candidemia up to 1.27/1000 admissions and 1.59/10,000 patient days was documented. In all the three surveys, Candida albicans remains the most frequently isolated species, ranging from 52 to 59 % of the etiology of BSIs. The epidemiological shift to the more resistant C. glabrata, observed between 1997-1999 and 2009 surveys, was not confirmed by our more recent data. The pattern of etiology of BSIs occurred in 2014-2015 overlaps that of the 90s. Acquired antifungal resistance is a rare event. No isolate had an amphoterin B minimal inhibitory concentration (MIC, mg/L) value higher than the epidemiological cutoff. All the echinocandin MIC distributions are typical for wild-type organisms except for those of two C. glabrata isolates. Fluconazole resistance declined from 24.9 % in the 2009 survey to 5.4 % in the recent one. CONCLUSIONS: Data from regional surveys may highlight the influence of therapeutic practices on the epidemiology of Candida BSIs and may optimize empirical therapies.
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Candida , Candidemia , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Candidemia/microbiología , Humanos , Italia/epidemiología , Pruebas de Sensibilidad Microbiana , Vigilancia en Salud PúblicaRESUMEN
Dermatomycoses due to Trichophyton violaceum are described in Mediterranean Countries, North Africa and in the Horn of Africa where T. soudanense is present too, but it was rare until few years ago in Italy. Aim of the present study was to evaluate an Italian multicenter 9 year (2005-2013) experience concerning these re-emerging pathogens. Fifty three fungal strains were sent from clinical laboratories to the Medical Mycology Committee (CoSM)--Italian Association of Clinical Microbiology (AMCLI) for mycological confirmation. Strains were identified as T. violaceum (23) and T. soudanense (30) by phenotypic and genotypic methods. These dermatophytes present epidemiological (high rate of inter-human transmission, high risk among adopted children coming from countries of either the Horn of Africa or Sub-Saharan Africa also in outbreaks of tinea capitis) and clinical peculiarities (reduced alopecia, presence of exudative lesions) confirming the originality of these "imported" dermatophyte infections.
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Tiña/microbiología , Trichophyton/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Italia/epidemiología , Masculino , Tiña/epidemiología , Trichophyton/genética , Trichophyton/fisiología , Adulto JovenRESUMEN
The authors evaluated the performance of the MycArray™ Yeast ID (Myconostica Ltd, UK) assay in the identification of a total of 88 yeast isolates recovered in culture as compared to that obtained through routine methods. The turn-around time for species identification directly from cultures by the MycArray was 6 hours, much quicker than classical methods and all yeasts were correctly identified. In two cases a double identification including Saccharomyces cerevisiae was noted, but it was not confirmed by culture. The results show that MycArray Yeast ID can be a potential tool for rapid detection and identification of Candida species.
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Sangre/microbiología , Fungemia/microbiología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Levaduras/clasificación , Levaduras/aislamiento & purificación , Candida/clasificación , Candida/genética , Candida/aislamiento & purificación , Medios de Cultivo , Hospitales , Humanos , Italia , Técnicas de Tipificación Micológica/instrumentación , Técnicas de Tipificación Micológica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Saccharomyces cerevisiae/clasificación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/aislamiento & purificación , Levaduras/genéticaRESUMEN
Fungaemia is an increasing nosocomial pathology. The 'gold standard' for detection of fungaemia is blood culture, but it is time-consuming and its sensitivity for early detection is low. On the other hand, yeasts present different antifungal sensitivity patterns to be quickly detected to allow an effective treatment. The aim of this study was to evaluate the diagnostic performances of PNA-FISH to directly identify yeasts from blood cultures and to compare results with those obtained by culture. A total of 176 blood cultures positive for yeasts at direct Gram stain and 24 negative blood cultures as control collected from 15 Italian hospitals, included in a network coordinated by the Medical Mycology Committee, Italian Society of Clinical Microbiology (AMCLI), were examined both by culture and PNA-FISH technology. Sensitivity of the PNA-FISH technique evaluated for five Candida species was 99.3% and specificity, 100%. Distinguishing which yeast is implicated in fungaemia and whether the infection is caused by multiple species are important for the selection of antifungal therapy. The PNA-FISH technique is a very useful approach because the test discriminates between groups of Candida species with different susceptibility pattern, particularly against azoles and echinocandins, with only a 90-minute turn-around time after the Gram-stain reading.
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Fungemia/microbiología , Hongos/clasificación , Hongos/aislamiento & purificación , Hibridación Fluorescente in Situ/métodos , Técnicas de Diagnóstico Molecular/métodos , Micología/métodos , Ácidos Nucleicos de Péptidos , Sangre/microbiología , Hospitales , Humanos , Italia , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
In this study the activity of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin against 224 clinical isolates of Aspergillus spp. originating from seven Italian hospitals, was comparatively evaluated with two commercial antifungal susceptibility tests (AST): SensititreTM YeastOneTM (SYO) and MIC Test Strip. More attention was focused on Isavuconazole activity, given the new introduction of the drug in widely distributed antifungal susceptibilities methods in the clinical microbiology lab. The minimum inhibitory concentrations of antifungal drug that can inhibit the growth of pathogen by 90% (MIC90) for Isavuconazole detected by SYO were 0.5, 1, 0.25, and 2 µg/mL for Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Aspergillus niger, respectively, whilst they were 0.25, 0.25, 0.5, and 0.75 µg/mL by MIC Test Strip. Essential agreement between the two tested methods for Isavuconazole is 70% for all the species tested, 75.7% for A. fumigatus, 45.2% for A. flavus, 90.6% for A. terreus, and 40% for A. niger. Although the tested strains do not express any phenotypic resistance, MIC results were quite different if tested with microdilution broth or gradient agar method. This is the first Italian multicenter report on Isavuconazole MIC obtained employing the widely used SensititreTM Yeast OneTM (SYO) and MIC Test Strip on clinical isolates of Aspergillus.
RESUMEN
BACKGROUND: Yeasts are a common cause of invasive fungal infections in critically ill patients. Antifungal susceptibility testing results of clinically significant fungal strains are of interest to physicians, enabling them to adopt appropriate strategies for empiric and prophylactic therapies. We investigated the antifungal susceptibility of yeasts isolated over a 2-year period from hospitalised patients with invasive yeast infections. METHODS: 638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC) and two co-ordinating centres (CC). The Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method was used at the CCs for comparison. RESULTS: Etest and Sensititre (LC/CC) MIC90 values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC90 values were influenced by the reduced susceptibility of Candida parapsilosis isolates to echinocandins and a reduced or lack of susceptibility of Candida glabrata and Candida krusei to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre), and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre); differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected. CONCLUSIONS: Our data confirm the different antifungal susceptibility patterns among species, and highlight the need to perform antifungal susceptibility testing of clinically relevant yeasts. With the exception of a few species (e.g. C. glabrata for azoles and C. parapsilosis for echinocandins), the findings of our study suggest that two of the most widely used commercial methods (Etest and Sensititre) provide valid and reproducible results.
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Antifúngicos/farmacología , Enfermedad Crítica , Micosis/microbiología , Levaduras/efectos de los fármacos , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Farmacorresistencia Fúngica , Humanos , Italia , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Levaduras/aislamiento & purificaciónRESUMEN
An interlaboratory evaluation (seven centers) of VITEK2 System and Sensititre YeastOne® was conducted to test the antifungal susceptibilities of yeasts. The MICs of amphotericin B, fluconazole, flucytosine, and voriconazole were determined for 70 isolates of Candida spp. Our results demonstrated a higher interlaboratory agreement of VITEK 2 System than Sensititre YeastOne©. A good concordance between the two methods was observed for amphotericin B, fluconazole, voriconazole and 5-fluorocytosine (from 81.4% to 88.6%). The study suggests the potential value of the VITEK2 System as a convenient alternative method for testing the susceptibility of yeasts. It also indicates the need for further optimization of MIC endpoint criteria to improve interlaboratory agreement.
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Antifúngicos/farmacología , Sangre/microbiología , Pruebas de Sensibilidad Microbiana/métodos , Micosis/microbiología , Levaduras/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana/instrumentación , Levaduras/aislamiento & purificaciónRESUMEN
BACKGROUND: Drug resistance is an emerging problem among streptococcal and enterococcal species. Automated diagnostic systems for species identification and antimicrobial susceptibility testing (AST) have become recently available. We evaluated drug susceptibility of clinical isolates of streptococci and enterococci using the recent Phoenix system (BD, Sparks, MD). Diagnostic tools included the new SMIC/ID-2 panel for streptococci, and the PMIC/ID-14 for enterococci. Two-hundred and fifty isolates have been investigated: beta-hemolytic streptococci (n = 65), Streptococcus pneumoniae (n = 50), viridans group streptococci (n = 32), Enterococcus faecium (n = 40), Enterococcus faecalis (n = 43), other catalase-negative cocci (n = 20). When needed, species ID was determined using molecular methods. Test bacterial strains were chosen among those carrying clinically-relevant resistance determinants (penicillin, macrolides, fluoroquinolones, glycopeptides). AST results of the Phoenix system were compared to minimal inhibitory concentration (MIC) values measured by the Etest method (AB Biodisk, Solna, Sweden). RESULTS: Streptococci: essential agreement (EA) and categorical agreement (CA) were 91.9% and 98.8%, respectively. Major (ME) and minor errors (mE) accounted for 0.1% and 1.1% of isolates, respectively. No very major errors (VME) were produced. Enterococci: EA was 97%, CA 96%. Small numbers of VME (0.9%), ME (1.4%) and mE (2.8%) were obtained. Overall, EA and CA rates for most drugs were above 90% for both genera. A few VME were found: a) teicoplanin and high-level streptomycin for E. faecalis, b) high-level gentamicin for E. faecium. The mean time to results (+/- SD) was 11.8 +/- 0.9 h, with minor differences between streptococci and enterococci. CONCLUSION: The Phoenix system emerged as an effective tool for quantitative AST. Panels based on dilution tests provided rapid and accurate MIC values with regard to clinically-relevant streptococcal and enterococcal species.
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Enterococcus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Streptococcus/efectos de los fármacos , Antibacterianos/farmacología , Automatización , Farmacorresistencia Bacteriana , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Infecciones Estreptocócicas/microbiología , Streptococcus/aislamiento & purificaciónRESUMEN
The purpose of this study was to verify the standard procedures and minimum level of knowledge of Italian public laboratories involved in the management of antifungal susceptibility testing (AST). Two nationwide surveys were performed in 1999 and 2004. One hundred and two Italian hospitals located in 85 provincial capitals (82.5%) participated to these surveys. In 1999, 28 (27.5%) laboratories versus 16 (15.7%) in 2004 stated that they did not perform any susceptibility testing. Some discrepancies observed in the survey confirm that AST is difficult to be correctly managed, and that it can be performed only in very well-trained centers. The great variability of the results of MIC determination and clinical interpretation underlines the urgent need to improve knowledge about indications, method choice, and interpretative criteria for AST both for clinical microbiologists and clinicians.
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Antifúngicos/farmacología , Técnicas de Laboratorio Clínico/normas , Hongos/efectos de los fármacos , Hospitales/normas , Pruebas de Sensibilidad Microbiana/normas , Femenino , Humanos , Italia , Manejo de Especímenes/métodos , Manejo de Especímenes/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Escherichia coli isolates collected at our Institution from 1999 to 2003 (n=20,258) were studied to evaluate the production of CTX-M-type extended-spectrum beta-lactamases (ESBL). Isolates suspected of producing CTX-M enzymes were analyzed by the double-disk synergy test, hybridization with specific probes, PCR and direct DNA sequencing. Overall, 53 ESBL-positive isolates were found to carry CTX-M-type genes (blaCTX-M-1, n=51; blaCTX-M-15, n=2). The isolation of CTX-M-positive strains increased from 1 per year (1999) to 26 per year (2003). The first isolate carrying the blaCTX-M-15 gene appeared in 2003 and was obtained from a patient previously treated with ceftazidime. CTX-M-positive isolates were characterized by multi-drug resistance and were obtained both from inpatients (n=29) and outpatients (n=24). Most patients were over 60-year-old (n=45), had underlying chronic diseases (n=32), and had been hospitalized more than once (n=33). Strains were frequently isolated from the urinary tract, often after recurrent infections. Our study demonstrates that CTX-M-producing isolates are increasing among E. coli strains. Adequate laboratory detection may help in choosing appropriate treatment and in limiting the spread of this resistance trait.
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Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Escherichia coli/efectos de los fármacos , Evolución Molecular , beta-Lactamasas/genética , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Preescolar , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Escherichia coli/enzimología , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiología , beta-Lactamasas/metabolismoRESUMEN
The treatment outcome of 35 cases of bacteremia due to Klebsiella pneumoniae isolates producing TEM-52 extended-spectrum beta-lactamase was studied. Twenty-eight cases, classified as "nonfatal disease" using the McCabe and Jackson classification, were investigated with regard to ciprofloxacin and imipenem response. Because ciprofloxacin was active in vitro against 21 of 28 isolates, only the treatment outcome of the ciprofloxacin-susceptible subgroup was evaluated. Eight of 10 cases occurred in patients who experienced a complete response to imipenem; 2 of 10 failed to respond. In contrast, only 2 of 7 cases had a partial response to ciprofloxacin, and, in 5 of 7 cases, the treatment failed. Statistical analysis revealed a significant difference in the treatment outcome of the 2 groups (P=.03). Because the isolates had minimum inhibitory concentrations of ciprofloxacin close to the susceptibility breakpoint, treatment failure could be ascribed to the inability of the drug to reach therapeutic concentrations at infected sites.
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Bacteriemia/tratamiento farmacológico , Ciprofloxacina/uso terapéutico , Imipenem/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae , beta-Lactamasas/análisis , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del Tratamiento , beta-Lactamasas/genéticaRESUMEN
A two-year analysis was performed at our hospital to evaluate the incidence and clinical impact of bloodstream infections (BSI) in medical, surgical, and intensive care unit patients. During 1999-2000 there were 521 cases of BSI with an incidence of 10.1/1,000 admissions. The most frequent predisposing factors for BSI were intravascular catheter (56.4%) and previous use of antibiotics (50.9%). Infections were considered as primary in 67.9% of cases. Urinary tract and intravascular catheter were the most frequent source of secondary bacteremia (43.1% and 35.9%, respectively). At the time of the first positive blood culture, 83.5% of patients were receiving empirical treatment, but it was adequate in only 53.9% of cases. After antimicrobial susceptibility testing, adequate antibiotic treatment was given in 67.9% of cases. Statistical analysis of independent risk factors showed that mortality was significantly related to age (P < 0.048), rapidly-fatal diseases (P < 0.001), septic shock (P < 0.020), multiorgan failure (P < 0.001), previous use of antibiotics (P < 0.008), Enterobacteriaceae producing extended-spectrum beta-lactamases (P < 0.036), and inadequate empirical treatment (P < 0.039). Based on local epidemiology and susceptibility data, microbiology laboratories should periodically release recommendations on the optimal empirical treatment for different wards.
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Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Antibacterianos/uso terapéutico , Causalidad , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The Phoenix system (Becton Dickinson Diagnostic Systems, Sparks, MD) was evaluated for identification (ID) to the species level of streptococci and enterococci. Two hundred clinical isolates were investigated: beta-hemolytic streptococci (n = 50), Streptococcus pneumoniae organisms (n = 46), viridans group streptococci (n = 31), Enterococcus faecium (n = 36), Enterococcus faecalis (n = 25), and other catalase-negative cocci (n = 12). The API system (bioMérieux, Marcy l'Etoile, France) was used as a comparator. Molecular methods (sequencing of 16S rRNA and zwf and gki genes and ddl gene amplification) were used to investigate discordant results. Upon resolution of discrepancies, correct species ID was achieved by the Phoenix system for 121/129 (93.8%) streptococci and 63/70 (90.0%) enterococci. Excellent results were obtained for S. pneumoniae (45/45) and beta-hemolytic streptococci (49/50). With regard to viridans streptococci, the accuracy of the Phoenix system was 83.9%. Among the latter organisms, the best performance was obtained with isolates of the Streptococcus sanguinis group and Streptococcus anginosus group; problems were instead encountered with the Streptococcus mitis group. Four E. faecium and three E. faecalis isolates were misidentified as Enterococcus casseliflavus/Enterococcus gallinarum or Enterococcus durans. Thus, these isolates were identified only at the genus level. Compared with commercially available systems, the Phoenix system appears a reliable diagnostic tool for identifying clinically relevant streptococci and enterococci. The SMIC/ID-2 panel proved particularly effective for beta-hemolytic streptococci and pneumococci.
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Técnicas de Tipificación Bacteriana , Enterococcus/clasificación , Juego de Reactivos para Diagnóstico , Streptococcus/clasificación , Automatización , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana/instrumentación , Técnicas de Tipificación Bacteriana/métodos , Técnicas de Laboratorio Clínico , Enterococcus/genética , Humanos , ARN Ribosómico 16S/genética , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Especificidad de la Especie , Streptococcus/genéticaRESUMEN
Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively uncommon clinical entity, and its significance has received little attention. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes due to P. mirabilis producing extended-spectrum beta-lactamases (ESBLs). Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period. Phenotypic and molecular methods were used to assess ESBL production. Clinical records of BSI patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe and Jackson classification and Charlson weighted index), risk factors, and treatment outcome were investigated by comparing cases due to ESBL-positive strains to cases due to ESBL-negative strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The remaining 14 isolates were ESBL negative and were uniformly susceptible to extended-spectrum cephalosporins and monobactams. Comparison of the two groups showed that previous hospitalization in a nursing home (P = 0.04) and use of bladder catheter (P = 0.01) were significant risk factors for infections due to ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a significantly higher mortality attributable to BSI (P = 0.04). BSI cases due to ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was associated with complete response independently of ESBL production. Therapeutic failure and mortality may occur in BSI episodes caused by ESBL-positive P. mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be critical for the clinical management of patients with systemic P. mirabilis infections.
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Antibacterianos/uso terapéutico , Bacteriemia , Infecciones por Proteus , Proteus mirabilis/efectos de los fármacos , beta-Lactamasas/metabolismo , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/mortalidad , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones por Proteus/tratamiento farmacológico , Infecciones por Proteus/epidemiología , Infecciones por Proteus/microbiología , Infecciones por Proteus/mortalidad , Proteus mirabilis/enzimología , Proteus mirabilis/patogenicidad , Factores de Riesgo , Resultado del Tratamiento , beta-Lactamasas/genéticaRESUMEN
Resistance to carbapenems is an emerging problem among gram-negative hospital pathogens. A transferable plasmid encoding the VIM-4 metallo-beta-lactamase was detected in isolates of Klebsiella pneumoniae and Enterobacter cloacae obtained from a single patient under carbapenem therapy. Thus, enterobacteria appear to increasingly contribute to the spread of VIM-type enzymes.
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Conjugación Genética/genética , Enterobacter cloacae/enzimología , Enterobacter cloacae/genética , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/genética , Plásmidos/genética , beta-Lactamasas/biosíntesis , beta-Lactamasas/genética , Anciano , Enterobacter cloacae/efectos de los fármacos , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Invasive aspergillosis is a serious problem for immunocompromised patients, especially if neutropenic. The diagnosis of this infection is complicated, since clinical symptoms are often similar to those of other fungal diseases. The chance of detecting the presence of a specific antigen in the serum could confirm the suspected clinical diagnosis and. perhaps, be useful for the follow-up of the patient. The Medical Mycology Committee of the Associazione Microbiologi Clinici Italiani (AMCLI) decided to evaluate in a multicenter prospective study (from I November 1998 to 28 February 1999) the performance of the Platelia Aspergillus Kit (Bio-Rad) for the detection of Aspergillus galactomannan in human serum. The enrolled patients included various groups of immunosuppressed patients (mostly neutropenic). Blood samples were drawn at the time of enrollment. This decision was based upon a clinical diagnosis of probable aspergillosis (antibiotic non-responsive fever for at least 96 hours, cough, hemophthosis and positive chest X-ray). Additional blood samples were drawn on days 3, 6, 9, 12, 15 and 21. Culture and histopathologic examinations were performed according to the individual laboratory workflow. For each patient the laboratory filled a form with all the available clinical information, to create a database on which to evaluate the results of the test. During the study, 187 patients with various kinds of immunosuppression were enrolled. A total of 256 sera were tested: for 117 patients (62.6%) only the basal sample was tested, whereas for the 70 symptomatic patients (37.4%) multiple specimens (range: 1-6) were tested. The results allowed the laboratories to exclude (68.6%) or confirm (31.5%: confirmed and/or probable) the clinical diagnosis of invasive aspergillosis; 4 cases remained undetermined. Based on the results of this study, it seems that the use of this test should be limited to those patients with clinical symptoms of aspergillosis.
Asunto(s)
Antígenos Fúngicos/análisis , Aspergilosis/diagnóstico , Aspergillus/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/métodos , Huésped Inmunocomprometido , Antígenos Fúngicos/sangre , Aspergilosis/sangre , Aspergilosis/etiología , Aspergilosis/inmunología , Aspergillus/inmunología , Estudios de Evaluación como Asunto , Femenino , Galactosa/análogos & derivados , Humanos , Masculino , Mananos/inmunología , Estudios Multicéntricos como Asunto , Neutropenia/inducido químicamente , Neutropenia/microbiologíaRESUMEN
Successful carbapenem-based chemotherapy for the treatment of Pseudomonas infections has been seriously hindered by the recent appearance of IMP- and VIM-type metallo-beta-lactamases, which confer high-level resistance to carbapenems and most other beta-lactams. Recently, multidrug-resistant Pseudomonas putida isolates for which carbapenem MICs were >/=32 micro g/ml were recovered from cultures of urine from three inpatients in the general intensive care unit of the Ospedale di Circolo, Varese, Italy. Enzyme assays revealed production of a metallo-beta-lactamase activity, while molecular analysis detected in each isolate a bla(VIM-1) determinant carried by an apparently identical medium-sized plasmid. Conjugation experiments were unsuccessful in transferring the beta-lactamase determinant to Escherichia coli or Pseudomonas aeruginosa. Macrorestriction analysis by pulsed-field gel electrophoresis demonstrated that the isolates were of clonal origin. PCR mapping and sequencing of the variable region of the plasmid-borne class 1 integron carrying the bla(VIM-1) determinant (named In110) showed that the bla(VIM-1)-containing cassette was identical to that previously found in strains of different species from other Italian hospitals and that the cassette array of In110 was not identical but clearly related to that of In70 (a bla(VIM-1)-containing plasmid-borne integron from an Achromobacter xylosoxidans isolate), pointing to a common origin of this cassette and to a related evolutionary history of their cognate integrons.