Duration of antibiotic therapy for Enterobacterales and Pseudomonas aeruginosa: a review of recent evidence.

PURPOSE OF REVIEW: Emergence of multidrug-resistant organisms, impact on intestinal microbiome, side effects and hospital costs are some of the factors that have encouraged multiple studies over the past two decades to evaluate different duration of antibiotic therapy with the goal of shorter but effective regimens. Here, we reviewed the most recent relevant data on the duration of therapy focused on two of the most common Gram-negative organisms in clinical practice, Pseudomonas aeruginosa and Enterobacterales. RECENT FINDINGS: Recent studies including meta-analysis confirm that short antibiotic courses for both Enterobacterales and P. aeruginosa infections have comparable clinical outcomes to longer courses of therapy. Despite the advocacy for short-course therapy in contemporary guidelines, recent evidence in the USA has revealed a high prevalence of inappropriate antibiotic usage due to excessive duration of therapy. SUMMARY: Although the decision process regarding the optimal duration of antibiotic therapy is multifactorial, the vast majority of infections other than endocardial or bone and joint, can be treated with short-course antibiotic therapy (i.e., ≤7 days). The combination of biomarkers, clinical response to therapy, and microbiologic clearance help determine the optimal duration in patients with infections caused by P. aeruginosa and Enterobacterales.

Fibroblast growth factor receptor 3 isoforms: Novel therapeutic targets for hepatocellular carcinoma?

UNLABELLED: Fibroblast growth factor receptors (FGFRs) are frequently up-regulated in subsets of hepatocellular carcinoma (HCC). Here, we provide mechanistic insight that FGFR3 splice variants IIIb and IIIc impact considerably on the malignant phenotype of HCC cells. The occurrence of FGFR3 variants was analyzed in human HCC samples. In hepatoma/hepatocarcinoma cell lines, FGFR3 isoforms were overexpressed by lentiviral constructs or down-modulated by small interfering RNA (siRNA; affecting FGFR3-IIIb and -IIIc) or an adenoviral kinase-dead FGFR3-IIIc construct (kdFGFR3). Elevated levels of FGFR3-IIIb and/or -IIIc were found in 53% of HCC cases. FGFR3-IIIb overexpression occurred significantly more often in primary tumors of large (pT2-4) than of small size (pT1). Furthermore, one or both isoforms were enhanced mostly in cases with early tumor infiltration and/or recurrence at the time of surgery or follow-up examinations. In hepatoma/hepatocarcinoma cells, up-regulated FGFR3-IIIb conferred an enhanced capability for proliferation. Both FGFR3-IIIb and FGFR3-IIIc suppressed apoptotic activity, enhanced clonogenic growth, and induced disintegration of the blood/lymph endothelium. The tumorigenicity of cells in severe combined immunodeficiency mice was augmented to a larger degree by variant IIIb than by IIIc. Conversely, siRNA targeting FGFR3 and kdFGFR3 reduced clonogenicity, anchorage-independent growth, and disintegration of the blood/lymph endothelium in vitro. Furthermore, kdFGFR3 strongly attenuated tumor formation in vivo. CONCLUSIONS: Deregulated FGFR3 variants exhibit specific effects in the malignant progression of HCC cells. Accordingly, blockade of FGFR3-mediated signaling may be a promising therapeutic approach to antagonize growth and malignant behavior of HCC cells.

Absence of Anti-Babesia microti antibody in commercial intravenous immunoglobulin (IVIG).

BACKGROUND: Babesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of Babesia microti antibodies in commercial samples of IVIG. METHODS/PRINCIPLE FINDINGS: The presence of B. microti antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for B. microti antibodies using an enzyme linked immunosorbent assay. Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for B. microti antibodies. CONCLUSIONS: Commercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.

Idiopathic Sclerosing Encapsulating Peritonitis in a Patient with Atypical Symptoms and Imaging Findings.

Sclerosing encapsulating peritonitis is a rare condition caused by a fibrotic membrane covering the small bowel which may lead to abdominal pain or obstruction. The cause may be primary and idiopathic or secondary to several diseases, treatments, and/or medications. The condition typically presents with bowel obstruction, and only one previous case has described ascites as the presenting sign. Sclerosing encapsulating peritonitis is typically diagnosed intraoperatively. We present a case of a patient who presented with atypical clinical symptoms including respiratory distress, recurrent abdominal ascites, and failure to thrive who was diagnosed nonoperatively.

Prosthetic valve endocarditis caused by Aerococcus Urinae.

Infective endocarditis (IE) caused by Aerococcus urinae is rare. The true incidence rate of this pathogen is likely underestimated as this is easily misidentified as Staphylococci or Streptococci. It is also associated with increased risk of complications such as systemic emboli. Aerococcus usually affects elderly males with underlying urological conditions. Here we present a case of IE with this rare Aerococcus urinae in a young man with a bioprosthetic aortic valve, despite negative urine cultures.

Lipid derivatives of arachidonic acid used as markers of atherosclerotic plaque instability: a pilot study.

BACKGROUND: To compare the results of computer estimation of atherosclerotic plaque with biochemical data and ascertain any relationship with the occurrence of stroke. METHODS: The study involved 20 atherosclerotic plaques causing 70-99% stenosis of internal carotid arteries (ICA). Ultrasonographic examination (USG) images of plaques were analyzed using a computer program. A histogram was obtained for each plaque and a gray scale median (GSM) was determined for each histogram in order to measure the echogenicity of an examined plaque. Then the plaques, collected during endarterectomy, were examined with regard to the concentration of prostaglandins E2 (PGE2), thromboxane A2 (TXA2), and 8 - epi-prostaglandin F2α. This data was compared with GSM and the occurrence of stroke. RESULTS: The statistical analysis showed significant correlations between low GSM and the occurrence of strokes. Out of 10 plaques with GSM<35, 6 (60.0%) were associated with a stroke. In contrast, out of 10 plaques with GSM>35, only 1 (10.0%) had a stroke. In addition, there were significant differences in the plaque content of PGE 2, (P<0.05) and (TXA2, P<0.011) between groups. CONCLUSIONS: High levels of PGE2 and TXA2, correlated with the low GSM values, may be the features of unstable plaques and that may be associated with a risk for stroke.