A Case-Control Study on the Association between Salmonella Bacteriuria and Cystoscopy.

To date, there is only one published report of an outbreak of urinary tract infections by Salmonella species after cystoscopy. Disinfection procedures for cystoscope have come into question. The current study aimed to determine the odds of developing Salmonella bacteriuria after cystoscopy. A retrospective case-control study was conducted on all patients with Salmonella species in urine (case) and blood (control) from 2017 to 2019 in 16 hospitals in Eastern Ontario, Canada. Eight of the 11 patients had cystoscopy prior to Salmonella bacteriuria; three of the 74 patients had urological procedures prior to Salmonella bacteremia, but none of their procedures were cystoscopy. The odds ratio of urological procedures with Salmonella bacteriuria was 63.1 (95% CI 10.9 to 366.6; p < 0.0001). In the bacteriuria group, the most frequently identified isolates were Salmonella enteritidis (n = 8), followed by Salmonella oranienburg, and Salmonella heidelberg. Seven of the S. enteritidis isolates had identical susceptibilities (ampicillin-sensitive; sulfamethoxazole/trimethoprim-sensitive; ciprofloxacin intermediate). In the bacteremia group, the most frequently identified isolates were S. enteritidis (n = 22), followed by Salmonella typhi, S. heidelberg, S. oranienburg, and Salmonella typhimurium. The result suggested cystoscopy is a risk factor for Salmonella bacteriuria. Identification of Salmonella bacteriuria should prompt public health investigations of linkage between cystoscopy and Salmonella bacteriuria.

A Case Series of Diarrheal Diseases Associated with Yersinia frederiksenii.

To date, Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis are the three Yersinia species generally agreed to be pathogenic in humans. However, there are a limited number of studies that suggest some of the "non-pathogenic" Yersinia species may also cause infections. For instance, Yersinia frederiksenii used to be known as an atypical Y. enterocolitica strain until rhamnose biochemical testing was found to distinguish between these two species in the 1980s. From our regional microbiology laboratory records of 18 hospitals in Eastern Ontario, Canada from 1 May 2018 to 1 May 2021, we identified two patients with Y. frederiksenii isolates in their stool cultures, along with their clinical presentation and antimicrobial management. Both patients presented with diarrhea, abdominal pain, and vomiting for 5 days before presentation to hospital. One patient received a 10-day course of sulfamethoxazole-trimethoprim; his Y. frederiksenii isolate was shown to be susceptible to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, and sulfamethoxazole-trimethoprim, but resistant to ampicillin. The other patient was sent home from the emergency department and did not require antimicrobials and additional medical attention. This case series illustrated that diarrheal disease could be associated with Y. frederiksenii; the need for antimicrobial treatment should be determined on a case-by-case basis.

Use of Pulsed-Field Gel Electrophoresis to Determine the Source of Methicillin-Resistant Staphylococcus aureus Bacteremia.

Pulsed-field gel electrophoresis (PFGE) has historically been considered the gold standard in fingerprinting bacterial strains in epidemiological studies and outbreak investigations; little is known regarding its use in individual clinical cases. The current study detailed two clinical cases in which PFGE helped to determine the source of their methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Patient A was found to have MRSA bacteremia after trauma in her pelvic area. MRSA was also found in her groin but not in her nostril and rectum. PFGE was performed that showed variable bands of her MRSA isolates from blood and groin, suggestive of different strains of MRSA. Her MRSA bacteremia was determined to be unrelated to her pelvic trauma. Patient B was found to have MRSA bacteremia after colonoscopy. MRSA was also found in his nostril and rectum. PFGE was performed that showed variable bands of his MRSA isolates from blood and rectum but identical bands of MRSA isolates from his blood and nostril. His MRSA bacteremia was determined to be unrelated to his colonoscopy procedure. The current study demonstrates the use of PFGE to rule out the source of bacteremia in individual clinical cases.

Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin.

Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[a]pyrene or 7,12-dimethylbenz[a]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen-bioactivating enzyme. Melatonin (3-300 microm) decreased 7-ethoxyresorufin O-dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7-hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparent K(i) values (mean +/- S.E.M.) of 59 +/- 1 (CYP1A1), 12 +/- 1 (CYP1A2), 14 +/- 2 (CYP1B1) and 46 +/- 8 microm (hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[a]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF-10A human mammary epithelial cells with melatonin (up to 300 microm) did not affect basal or benzo[a]pyrene-inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor-dependent pGudluc6.1-transfected MCF-10A cells treated with or without benzo[a]pyrene, as assessed in an in vitro cell-based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1-mediated chemical carcinogenesis.

First case report of infective endocarditis associated with Microbacterium maritypicum.

Microbacterium species are gram positive coryneforms generally considered as a contaminant when identified in gram stain of blood culture, especially when time-to-positivity is longer than 48 h. We encountered a case of infective endocarditis associated with Microbacterium maritypicum bacteremia, which became positive after 48 h of incubation in three out of four bottles. The antimicrobial management is controversial as vancomycin is generally assumed to cover most gram positive bacilli, but our susceptibility result demonstrated minimum inhibitory concentration of 4 µg/mL of vancomycin, indicating non-susceptibility. To the best of our knowledge, this is the first case report of infective endocarditis associated with Microbacterium maritypicum.

Identification of Ginkgo biloba as a novel activator of pregnane X receptor.

Pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a role not only in drug metabolism and transport but also in various other biological processes. Ginkgo biloba is a herbal medicine commonly used to manage memory impairment. Treatment of primary cultures of rat hepatocytes with G. biloba extract increases the mRNA expression of CYP3A23, which is a target gene for rat PXR. The present study was conducted to test the hypothesis that G. biloba extract activates PXR. Treatment of mouse PXR (mPXR) or human PXR (hPXR)-transfected HepG2 cells with G. biloba extract at 200 microg/ml increased mPXR and hPXR activation by 3.2- and 9.5-fold, respectively. Dose-response analysis showed a log-linear increase in hPXR activation by the extract over the range of 200 to 800 microg/ml. To determine whether G. biloba extract induces hPXR target gene expression, cultured LS180 human colon adenocarcinoma cells were treated for 72 h with the extract. G. biloba extract at 200, 400, and 800 microg/ml increased CYP3A4 mRNA expression by 1.7-, 2.4-, and 2.5-fold, respectively. The same concentrations of the extract increased CYP3A5 (1.3-3.6-fold) and P-glycoprotein (ABCB) 1 (2.7-6.4-fold) mRNA expression. At concentrations (5 and 10 microM) that did not down-regulate PXR gene expression and were not cytotoxic, L-sulforaphane (an hPXR antagonist) decreased CYP3A4, CYP3A5, and ABCB1 gene expression in cells treated with G. biloba extract. In summary, G. biloba extract activated mPXR and hPXR in a cell-based reporter gene assay and induced CYP3A4, CYP3A5, and ABCB1 gene expression in hPXR-expressing LS180 cells.

Pharmacists Becoming Physicians: For Better or Worse?

Physicians and pharmacists nowadays are often described as adversaries rather than members of the same team. Some pharmacists apply to medical school later in their careers, and experience obstacles during the transition process. This article details interviews with two physician⁻pharmacists, who each have a past pharmacist license and current physician license. The respondents described the limitations of pharmacists' scope of practice as their main reasons to pursue a medical career. However, the respondents enjoy applying their pharmacy knowledge and experience to improve their medical practice. They do not feel pharmacy seniors and medical recruiters are supportive towards their chase for medical careers. The respondents noted the importance of peer-reviewed articles to promote pharmacist involvement in patient care and collaboration between physicians and pharmacists. Conflicts between physicians and pharmacists tend to happen because of their different focuses on patient care. The respondents do not see themselves having an edge over other medical school applicants, and noted that recruiters could negatively view their pharmacy experience. The respondents believe that physician⁻pharmacists are catalysts to foster collaboration between physicians and pharmacists, because they clearly understand the role of each profession. Nevertheless, the respondents feel that physicians and pharmacists are generally lukewarm towards pharmacists transitioning into physicians.

Is Research Experience Detrimental to a Clinical Pharmacist's Career?

A recent article in the Canadian Journal of Hospital Pharmacy discussed pharmacists' perception of clinical research. The article illustrated that pharmacists lack the time, resources, and skills to conduct research. In the current paper, two ex-pharmacists, who now work as physicians, commented on the prejudice towards pharmacy researchers. Pharmacy researchers face obstacles such as being mislabeled as "non-clinical" and lacking opportunities to be involved in high-impact publications. The current paper discussed ways to improve pharmacy research, including collaboration with well-established researchers, putting less emphasis on the "clinical" pharmacist title, and changing the pharmacy culture.