Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds.

Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from patients newly identified as nasal carriers.

We aimed to determine whether additional molecular and microbiological evaluations of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients newly identified as nasal carriers were useful for control strategies and whether longitudinal testing during the same or repeat hospitalization changed MRSA status. Nasal swabs from patients positive by Xpert MRSA PCR and not known to be colonized in the previous year were cultured for S. aureus. Isolates were tested for resistance to a variety of antibiotics, including high-level mupirocin resistance (HLMR) and low-level mupirocin resistance (LLMR) and the presence of genes mecA and mupA and those for Panton-Valentine leukocidin (PVL), USA300, and USA400. Repeat nasal screens during the 6-month study were tested for continued presence of MRSA. Among 130 patients, cultures revealed MRSA in 85 (65.4%), methicillin-susceptible S. aureus in 19 (14.6%), and no growth in 26 (20%). MRSA isolates were USA300 positive in 13/85 (15.3%) and LLMR in 8/85 (9.4%) patients. No isolates were HLMR or mupA positive. mecA dropout was detected in 9/130 (6.9%) patients. The rate of subsequent MRSA infections in USA300-positive versus -negative patients was not different. MRSA nasal status remained concordant in 69/70 (98.6%) patients who had follow-up testing. The findings do not support expanding MRSA surveillance to include routine detection of genes for USA300, PVL, or mupA, all of which were either of low frequency or not significantly associated with MRSA infection risk in our population of newly identified nasal carriers. Repeat nasal screening for MRSA during the same or subsequent hospitalizations over 6 months could also be deferred, reducing costs associated with screening.

Cohorting based on nasal methicillin-resistant Staphylococcus aureus status: an opportunity to share more than a room.

BACKGROUND: Hospital roommates are cohorted with similarly colonized patients to decrease methicillin-resistant Staphylococcus aureus (MRSA) transmission risk. However, little is known about differences in S aureus nasal and extranasal carriage between hospital roommates who are in MRSA or non-MRSA designated rooms. METHODS: Patients sharing hospital rooms were cultured for S aureus in the nose, throat, and other body sites. Differences in S aureus methicillin and mupirocin susceptibility and USA300 type were evaluated. RESULTS: Eighty-two patients comprising 48 roommate pairs were studied. Among 6 roommate pairs in MRSA rooms, 3 (50%) had differences in carriage based on having methicillin-susceptible S aureus at an extranasal body site. In non-MRSA rooms, 19 (45%) roommate pairs had differences in S aureus carriage. Extranasal colonization was significantly associated with discordance between roommates, P < .001. Antibiotic exposure, ward type, and the duration of room sharing were not associated with discordance. CONCLUSION: Patients have almost a 50% chance of having differences in S aureus colonization compared with their hospital roommate, even in MRSA-designated rooms. Cohorting by MRSA status at the time of admission may not be as effective a control strategy as horizontal measures that do not rely on known colonization with S aureus or other pathogens.

'Bald trochanter' spontaneous rupture of the conjoined tendons of the gluteus medius and minimus presenting as a trochanteric bursitis.

A 66-yr-old white woman presented with progressive complaints of right lateral hip and thigh pain associated with a disabling limp without an antecedent history of trauma. Physical examination revealed localized pain over the right greater trochanter to palpation. A full pain-free range of motion of the right hip was associated with weakness in the hip abductors. The patient ambulated with a compensated right Trendelenburg gait. Subsequent magnetic resonance imaging demonstrated a trochanteric bursitis and an effusion of the hip and a full-thickness tear of the gluteus medius muscle, with both a disruption and retraction of the tendon of an atretic gluteus minimus muscle. Conjoined tendon pathology of both the gluteus medius and minimus as, revealed by magnetic resonance examination, is probably more frequent than heretofore commonly recognized. In patients presenting with "intractable" complaints of a trochanteric bursitis and an ambulatory limp due to weakness in the hip abductors, imaging studies calling attention to a possible tendon rupture may be diagnostic.