We report two cases of Nocardia cyriacigeorgica septicemia and disseminated infection in the setting of profound immunodeficiency. In both instances, diagnosis was rapidly facilitated by 16S rRNA gene sequencing of blood culture isolates. These constitute the first confirmed reports of Nocardia cyriacigeorgica bloodstream infection in humans.CASE REPORTS Case 1. The patient was a 69-year-old woman with type 2 diabetes mellitus, chronic lymphocytic leukemia, and hypogammaglobulinemia who presented to hospital "A" with a 3-week history of malaise, right-sided flank and pleuritic chest discomfort, left leg weakness, and an ataxic gait. She denied any fever, chills, cough, or weight loss. Baseline laboratory studies revealed neutrophilia, lymphocytosis, anemia, and hyponatremia. Radiologic studies demonstrated patchy and nodular infiltrates in the right lung, bilateral pleural effusions, multiple ring enhancing lesions in the cerebellum and cerebrum, and a right adrenal mass. Upon the patient's admission to hospital, three sets of BacT/Alert FAN (bioMerieux Inc., Durham, N.C.) aerobic and anaerobic blood cultures were collected, while the adrenal mass was biopsied to rule out infectious and noninfectious etiologies. After 2.5 days of incubation, the aerobic bottle of one of the blood culture sets demonstrated the presence of a partially acid fast, branching, rod-shaped bacterium that formed dry white colonies after overnight growth on 5% sheep blood and Sabouraud dextrose agar media. Respiratory samples were not collected for microbiological analysis. A diagnosis of disseminated nocardiosis was subsequently made, after which the patient received empirical therapy with intravenous meropenem (1 g every 8 h) and oral trimethoprim-sulfamethoxazole (TMP-SMX) (160 and 800 mg, respectively, twice daily). Using Microseq 500 kits and an ABI Prism 3100 genetic analyzer (Applied Biosystems, Foster City, CA), partial sequencing (first 500 bp) of the 16S rRNA gene of the blood culture was successful. A BLAST search (http://www.ncbi.nlm.nih.gov/BLAST/) of the GenBank database revealed 100% homology of our patient's sequence with that of five strains of Nocardia cyriacigeorgica (GenBank accession numbers AB094578, AB115955, AY244782, AY262326, and AB094580) and 98.1% and 97.9% homology with two other N. cyriacigeorgica strains (GenBank accession numbers AF430027 and AF282889, respectively). The adrenal biopsy culture was also positive for N. cyriacigeorgica. The isolate was susceptible to TMP-SMX (MICs, Յ2/38 g/ml), imipenem (MIC, 2 g/ml), and amikacin (MIC, Յ16 g/ml) based on Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) broth microdilution susceptibility testing (13). The patient's clinical condition gradually improved over the course of her stay in the hospital, but she remained on intravenous meropenem and oral TMP-SMX for several weeks thereafter through the regional home intravenous therapy program. Follow-up radiologic investigations 2 months post-hospital discharge demonstrated complete resolution of t...

The antibiotics known as aminoglycosides are commonly used to treat severe infections caused by Gram-negative bacteria. Unfortunately, they often lead to acute renal failure after their accumulation in the lysosomes of renal cells, where an inhibition of the phospholipid catabolism is observed. The lipopeptidic antibiotic daptomycin has been shown to reduce the nephrotoxicity of aminoglycosides, but the exact mechanism of this protection is still unknown. In the present study, Fourier transform infrared spectroscopy (FTIR) has been used to monitor the hydrolysis of phosphatidylcholine by phospholipase A2 (PLA2) from Naja mocambique mocambique venom in the presence of various aminoglycosides and/or daptomycin. Gentamicin and amikacin inhibited the reaction in its early stage. Kanamycin A, tobramycin, and especially kanamycin B enhanced the initial enzyme activity by reducing the lag time. After the initiation period, the reaction proceeded at a much slower rate in the presence of gentamicin. On the other hand, daptomycin led to dramatic alterations of the hydrolysis profile: the initial latency period was eliminated, and the maximal extent of hydrolysis was reduced. When both daptomycin and any of the aminoglycosides were present, the latency period also disappeared, and the phospholipase activity was higher than with the lipopeptide alone. The most drastic change occurred with gentamicin, which was the most inhibitory aminoglycoside when used alone but worked synergistically with daptomycin to yield the most dramatic activation of PLA2.