Immunosuppression and Opportunistic Infections: A Rare Case Report of Nocardia Osteomyelitis of the Pelvis.

Patients with a long-standing history of immunosuppression are at significantly increased risk of opportunistic infections. One such group of organisms that may cause these types of infections includes the Nocardia genus, a gram-positive, filamentous rod that demonstrates a branching pattern, is urease-producing and has acid-fast properties. The disease profile of Nocardia varies with manifestations ranging from cutaneous infection to severe pulmonary or central nervous system (CNS) infections, and rarely, osteomyelitis. In this case report, we present an 87-year-old female with persistent left gluteal and lumbar pain, generalized body aches, chills, and fevers diagnosed with Nocardia asiatica osteomyelitis of the pelvis, likely secondary to dissemination from pulmonary cavitary disease in an immunosuppressed host with chronic neutropenia. On magnetic resonance imaging (MRI), the patient was found to have heterogeneous enhancement, central necrosis, and loss of cortical margins of the left iliac wing, alongside a rim-enhancing soft tissue mass from the left iliac bone into the left gluteal soft tissues and left paraspinal musculature representing an abscess. She was promptly treated with surgical irrigation and drainage with surgical wound cultures growing Nocardia asiatica. She received treatment with trimethoprim-sulfamethoxazole antibiotics with symptom improvement and is following up with an infectious disease physician outpatient. Management of osteomyelitis, like in this case, involves long-term antibiotics with the potential need for surgical intervention. There are few reported cases of extrapulmonary Nocardia infections, particularly osteomyelitis, demonstrating the importance of their inclusion in the literature to better serve patients to allow for timely intervention for rare and life-threatening conditions. In immunocompromised hosts, the differential diagnosis should include opportunistic infections and less common pathogens, especially in those with atypical presentations, including gluteal and leg pain.

Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents.

A series of cystargolide-based ß-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue 8g, containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC50 = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.

Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multidrug-Resistance Proteins.

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.

Congenital Chagas' disease transmission in the United States: Diagnosis in adulthood.

Two brothers with congenitally-acquired Chagas' disease (CD) diagnosed during adulthood are reported. The patients were born in the USA to a mother from Bolivia who on subsequent assessment was found to be serologically positive for Trypanosoma cruzi. Serologic screening of all pregnant women who migrated from countries with endemic CD is strongly recommended.

Approaches to vancomycin-resistant enterococci.

PURPOSE OF REVIEW: This article reviews recent publications regarding new antimicrobial drugs for the treatment of vancomycin-resistant enterococci. RECENT FINDINGS: Newer drugs against vancomycin-resistant enterococci are now available or will soon be available. Quinupristin-dalfopristin, a streptogramin, and linezolid, an oxazolidinone, are effective and safe but only bacteriostatic against enterococi. Bacterial isolates resistant to either antibiotic have been described. Daptomycin, a lipopeptide antimicrobial, has good in-vitro bactericidal activity against enterococci, but very limited clinical data exist regarding the treatment of serious enterococcal infection with this compound. Ramoplanin, the first glycolipodepsipeptide antimicrobial in clinical trials, is not systemically absorbed after oral administration, and is being evaluated for the prevention of bloodstream infection in patients colonized with vancomycin-resistant enterococci. Oritavancin and dalbavancin (both glycopeptides) and tigecycline (a monocycline derivative) are being evaluated in phase II and III trials and are not yet commercially available. SUMMARY: Treatment of vancomycin-resistant enterococci continues to be problematical although these new drugs offer some hope. The rational use of antibiotics, strict guidelines for the use of new compounds, and adherence to infection control practices continue to be essential components of the management of vancomycin-resistant enterococci colonization and infection.