Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis.

ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1 → 3)-ß-D-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1 → 3)-ß-D-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.

Rapid ertapenem susceptibility testing and Klebsiella pneumoniae carbapenemase phenotype detection in Klebsiella pneumoniae isolates by use of automated microscopy of immobilized live bacterial cells.

We evaluated detection of ertapenem (ETP) resistance and Klebsiella pneumoniae carbapenemase (KPC) in 47 Klebsiella pneumoniae isolates using a novel automated microscopy system. Automated microscopy correctly classified 22/23 isolates as ETP resistant and 24/24 as ETP susceptible and correctly classified 21/21 isolates as KPC positive and 26/26 as KPC negative.

Stachybotrys eucylindrospora isolated from foreign material following a traumatic eye injury.

Stachybotrys eucylindrospora was characterised as a new species in 2007, and we present the first report of this organism isolated from foreign material recovered from a patient. It is probable that isolates of this species have been previously identified as either Stachybotrys chartarum or Stachybotrys cylindrospora.

Development and evaluation of a calibrator material for nucleic acid-based assays for diagnosing aspergillosis.

Twelve laboratories evaluated candidate material for an Aspergillus DNA calibrator. The DNA material was quantified using limiting-dilution analysis; the mean concentration was determined to be 1.73 × 10(10) units/ml. The calibrator can be used to standardize aspergillosis diagnostic assays which detect and/or quantify nucleic acid.

Detection of inducible clindamycin resistance in beta-hemolytic streptococci by using the CLSI broth microdilution test and erythromycin-clindamycin combinations.

This study assessed an erythromycin-clindamycin (ERY-CC) broth test for inducible CC resistance in beta-hemolytic streptococci. One hundred one isolates of groups A, B, C, F, and G were tested by the CLSI broth microdilution method. Combinations of 1 and 0.25 microg/ml or 0.5 and 0.25 microg/ml of ERY and CC, respectively, detected all inducible isolates.

Mechanisms of carbapenem resistance among a collection of Enterobacteriaceae clinical isolates in a Texas city.

Fourteen Enterobacteriaceae isolates with ertapenem MIC >2 mg/mL were analyzed to identify mechanisms of resistance. All isolates produced extended-spectrum beta-lactamase or AmpC beta-lactamase with variable, but decreased, expression of outer membrane proteins. One Enterobacter cloacae produced derepressed AmpC beta-lactamase, 1 Escherichia coli expressed plasmid-mediated AmpC beta-lactamase, and 1 E. cloacae produced a carbapenemase.

Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta-lactamases.

Effective therapeutic options are needed for community-onset urinary tract infections due to Escherichia coli strains that produce CTX-M extended-spectrum beta-lactamases. We examined 46 urinary isolates producing CTX-M against several oral or long-acting parenteral antimicrobial agents. Approximately 90% were susceptible to fosfomycin and to a combination of cefdinir plus amoxicillin-clavulanate. All were susceptible to ertapenem.

KPC-2-producing Enterobacter cloacae and pseudomonas putida coinfection in a liver transplant recipient.

Carbapenemases are among the newest resistance mechanisms to emerge in some gram-negative bacteria. We describe bacteremia in a critically ill liver transplant recipient infected with KPC-2-producing Enterobacter cloacae and Pseudomonas putida. Although this enzyme has been previously described in Enterobacter spp., this is the first report of KPC carbapenemase in P. putida.

Assessment of Aspergillus fumigatus burden in pulmonary tissue of guinea pigs by quantitative PCR, galactomannan enzyme immunoassay, and quantitative culture.

Early diagnosis of invasive pulmonary aspergillosis is problematic in some patient groups due to the lack of rapid, sensitive, specific, and reliable diagnostic tests. Fungal burden and therapeutic efficacy were assessed by survival, quantitative culture (CFU counts), galactomannan enzyme immunoassay (GM-EIA), and quantitative PCR (qPCR) in a new guinea pig model of invasive pulmonary aspergillosis using an aerosol challenge. At 1 day postinfection, qPCR determined that the pulmonary fungal burden was 2 log(10) higher than that determined by CFU counting and increased significantly (P < 0.03) over time. In contrast, the tissue burden assessed by CFU counting did not rise over the course of the study. Therapy with the antifungal drug voriconazole produced statistically significant decreases in pulmonary fungal burden, as detected by CFU counting (P < 0.02), qPCR, and GM-EIA (both P < 0.0002). Daily assessment of the progression of fungal infection in serum was performed by qPCR and GM-EIA. GM-EIA demonstrated a statistically significant reduction in the fungal load on days 6 and 7 in voriconazole-treated animals compared to time-matched controls (P < 0.02). Confirmation of fungal tissue burden by two or more methods should provide a more precise account of the burden, allowing improved assessment of diagnostic and therapeutic strategies in invasive pulmonary aspergillosis.