Effect of Clindamycin on Aminoglycoside Activity in a Murine Model of Invasive Escherichia coli Infection

Leucinostatin, an antimicrobial and antitumor antibiotic, was found to be cytotoxic to the murine leukemic cell line, L 1210. A complete inhibition of cell growth was achieved with 0.5 μg of the drug per ml. Leucinostatin showed membrane damage against L 1210 cells as well as mouse erythrocytes. L 1210 cells were partially protected from membrane damage by the addition of glucose to the medium. In contrast, no protective effect of glucose was observed with drug-induced hemolysis. The possible involvement of membrane lipid in the mechanism of action of leucinostatin is suggested by its action on liposomes. Liposomes prepared with lecithin, cholesterol, and an amphiphatic molecule, either dicetyl phosphate or stearylamine, were sensitive to leucinostatin and response to the drug was enhanced as the cholesterol level of liposomes was decreased. Changes in the net charge of the membrane did not show significant effects on leucinostatin action. In the presence of the antibiotic, on the other hand, protein synthesis in cells was markedly inhibited under conditions where the uptake of amino acids into an acid-soluble pool was not affected. However, leucinostatin did not exhibit any inhibitory effect on protein synthesis in a cell-free system from L 1210 cells. It is suggested that the inhibition of protein synthesis results from the initial interaction of the drug with membrane phospholipid.     

Burden of Fluoroquinolone Resistance in Clinical Isolates of Escherichia coli at the Ho Teaching Hospital,Ghana

BackgroundThe growing burden of antibiotic resistance is a threat to the management of infections. Infections by Escherichia coli are routinely treated with fluoroquinolone antimicrobial agents. Due to their frequent use, there has been increasing resistance to these drugs. We set out to determine the burden of fluoroquinolone resistance among clinical E. coli isolates at the Ho Teaching Hospital, Ghana.MethodsThis was a cross-sectional study conducted from July 2018 to June 2019. One hundred and thirty-five E. coli isolates were cultured from various clinical samples. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method with discs of nalidixic acid (NAL), ciprofloxacin (CIP), norfloxacin (NOR) and levofloxacin (LEV). Deoxyribonucleic acid (DNA) was extracted from the resistant isolates for the detection of fluoroquinolone resistant genes by polymerase chain reaction.ResultsNinety of the 135 isolates (66.7%) were resistant to at least one of the four fluoroquinolone drugs investigated. Resistance to NAL, CIP, NOR, and LEV was 51.0%, 51.1%, 38.8% and 35.7% respectively. Out of the fluoroquinolone resistant isolates, 69 carried one or more fluoroquinolone resistant genes. The predominant resistant genes were aac(6′)-Ib-cr (48.9%) and qnrD (25.6%). Seven of the isolates carried both qnrS and aac(6′)-Ib-cr genes. Two isolates carried 5 different fluoroquinolone resistant genes.ConclusionHigh prevalence of resistance to 4 fluoroquinolone drugs was recorded with associated resistant genes. This is a threat to current efforts to control the spread of antibiotic resistance and calls for concerted efforts to curb the spread of these resistant organisms.     

Photoacoustic radar phase-filtered spatial resolution and co-registered ultrasound image enhancement for tumor detection

Co-registered ultrasound (US) and frequency-domain photoacoustic radar (FD-PAR) imaging is reported for the first time in this paper. The merits of ultrasound and cross-correlation (radar) frequency-domain photoacoustic imaging are leveraged for accurate tumor detection. Commercial US imagers possess sophisticated, optimized software for rapid image acquisition that could dramatically speed-up PA imaging. The PAR image generated from the amplitude of the cross-correlation between detected and input signals was filtered by the standard deviation (SD) of the phase of the correlation signal, resulting in strong improvement of image spatial resolution, signal-to-noise ratio (SNR) and contrast. Application of phase-mediated image improvement is illustrated by imaging a cancer cell-injected mouse. A 14–15 dB SNR gain was recorded for the phase-filtered image compared to the amplitude and phase independently, while ~340 μm spatial resolution was seen for the phase PAR image compared to ~840 μm for the amplitude image.OCIS codes: (170.5120) Photoacoustic imaging, (170.3880) Medical and biological imaging, (170.7170) Ultrasound, (170.7180) Ultrasound diagnostics, (100.0100) Image processing     

The Combination of Insulin-Like Growth Factor Receptor 1 (IGF1R) Antibody Cixutumumab and Mitotane as a First-Line Therapy for Patients with Recurrent/Metastatic Adrenocortical Carcinoma: a Multi-institutional NCI-Sponsored Trial

Adrenocortical carcinoma (ACC) is an aggressive malignancy, which lacks an effective systemic treatment. Abnormal activation of insulin-like growth factor receptor 1 (IGF1R) has been frequently observed. Preclinical studies demonstrated that pharmacological inhibition of IGF1R signaling in ACC has antiproliferative effects. A previous phase I trial with an IGF1R inhibitor has demonstrated biological activity against ACC. The objective of this study is to assess the efficacy of the combination of the IGF1R inhibitor cixutumumab (IMC-A12) in association with mitotane as a first-line treatment for advanced/metastatic ACC. We conducted a multicenter, randomized double-arm phase II trial in patients with irresectable recurrent/metastatic ACC. The original protocol included two treatment groups: IMC-A12 + mitotane and mitotane as a single agent, after an initial single-arm phase for safety evaluation with IMC-A12 + mitotane. IMC-A12 was dosed at 10 mg/kg intravenously every 2 weeks. The starting dose for mitotane was 2 g daily, subsequently adjusted according to serum levels/symptoms. The primary endpoint was progression-free survival (PFS) according to RECIST (Response Evaluation Criteria in Solid Tumors). This study was terminated before the randomization phase due to slow accrual and limited efficacy. Twenty patients (13 males, 7 females) with a median age of 50.2 years (range 21.9–79.6) were enrolled for the single-arm phase. Therapeutic effects were observed in 8/20 patients, including one partial response and seven stable diseases. The median PFS was 6 weeks (range 2.66–48). Toxic events included two grade 4 (hyperglycemia and hyponatremia) and one grade 5 (multiorgan failure). Although the regimen demonstrated activity in some patients, the relatively low therapeutic efficacy precluded further studies with this combination of drugs.