Nocardia cyriacigeorgica is a recently characterized species within the genus of Nocardia. We report a brain abscess, following a primary pulmonary colonization, due to this species in a human immunodeficiency virus-infected patient. This case confirms that isolation of Nocardia in sputum is associated with a high risk of disseminated infection in immunocompromised patients. CASE REPORTA sub-Saharan 33-year-old human immunodeficiency virus (HIV)-infected woman was admitted for a generalized seizure in April 2004. Six months prior to admission, HIV infection had been diagnosed when she presented with weight loss, fever, cough, dyspnea, and chest pain. The CD4 lymphocyte count was 20 cells/mm 3 . Diagnosis of cavitary pneumonia due to Actinomyces sp. was established by culture of a bronchoscopic sample. She received oral treatment with amoxicillin at 150 mg/kg of body weight per day and minocycline at 100 mg twice a day. She also received primary prophylaxis for pneumocystosis with co-trimoxazole (one double-strength tablet per day) and highly active antiretroviral therapy with didanosine, lamivudine, and lopinavir-ritonavir. The patient was compliant with this regimen, which was associated with a global improvement of her clinical status, and the pneumonia was cured. Five months later, a new sputum sample grew Nocardia cyriacigeorgica. At that time she was asymptomatic, with no evidence of active pneumonia. The immune condition of the patient had also improved with a CD4 lymphocyte count at 80 cells/mm 3 . No change in therapy was made, based on a presumption of respiratory tract colonization by Nocardia. The follow-up sputum cultures did not grow the pathogen.On the day of her admission, she suddenly presented a grand mal seizure. A brain computed tomography scan showed a single ring enhancing nodular hyperdensity, surrounded by an edema, in the right frontal lobe which was confirmed by magnetic resonance imaging. A biopsy was first considered hazardous to perform. The diagnosis of toxoplasmosis abscess was unlikely because of primary prophylaxis with co-trimoxazole with good compliance, negativity of toxoplasmosis serology, and negativity of toxoplasmosis cerebrospinal fluid PCR assay. Because of a presumptive diagnosis of Actinomyces brain abscess, amoxicillin and minocycline therapy was continued, but oral amoxicillin was switched to intravenous administration at a dose of 200 mg/kg per day. However, the patient presented a progressive right arm paresis and new episodes of generalized seizure despite anticonvulsant therapy. Two weeks later, the follow-up brain magnetic resonance imaging showed a progression of the right frontal abscess and three new abscesses in the left cerebral hemisphere. A stereotaxial brain biopsy of the frontal abscess was performed. Direct sample examination by microscopy showed many polymorphonuclear leukocytes without any bacteria, but the culture grew a branched gram-positive rod organism, which was further identified as N. cyriacigeorgica. Antimicrobial therapy was changed to imipe...

Enterobacter cloacae CHE, a clinical strain with overproduced cephalosporinase was found to be highly resistant to the new cephalosporins, cefepime and cefpirome (MICsv128 Wg ml 31 ). The strain was isolated from a child previously treated with cefepime. The catalytic efficiency of the purified enzyme with the third-generation cephalosporins, cefepime and cefpirome, was 10 times higher than that with the E. cloacae P99 enzyme. This was mostly due to a decrease in K m for these L-lactams. The clinical isolate produced large amounts of the cephalosporinase because introduction of the ampD gene decreased ampC expression and partially restored the wild-type phenotype. Indeed, MICs of cefepime and cefpirome remained 10 times higher than those for a stable derepressed clinical isolate (OUDhyp) transformed with an ampD gene. Sequencing of the ampC gene showed that 18 nucleotides had been deleted, corresponding to the six amino acids SKVALA (residues 289^294). According to the crystal structure of P99 L-lactamase, this deletion was located in the H-10 helix. The ampR-ampC genes from the clinical isolates CHE and OUDhyp were cloned and expressed in Escherichia coli JM101. The MICs of cefpirome and cefepime of E. coli harboring ampC and ampR genes from CHE were 100^200 times higher than those of E. coli harboring ampC and ampR genes from OUDhyp. This suggests that the deletion, confirmed by sequencing of the ampC gene, is involved in resistance to cefepime and cefpirome. However, the high level of resistance to cefepime and cefpirome observed in the E. cloacae clinical isolate was due to a combination of hyperproduction of the AmpC L-lactamase and structural modification of the enzyme. This is the first example of an AmpC variant conferring resistance to cefepime and cefpirome, isolated as a clinical strain. ß

Enterobacter aerogenes resistant to cefepime (MIC, 32 microg/ml) was isolated from a patient treated with cefepime for an infection caused by a strain of E. aerogenes overproducing its AmpC beta-lactamase (MIC of cefepime, 0.5 microg/ml). The AmpC beta-lactamase of the resistant strain had an L-293-P amino acid substitution and a high k(cat)/K(m) ratio for cefepime. Both of these modifications were necessary for resistance to cefepime.