Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our findings suggest a mechanism of antibiotic killing that stems from the antibiotic’s ability to increase the pH within bacterial cells by disrupting proton entry without affecting proton pumping out of cells. Knowledge of the core mechanism necessary for antibiotic killing could have a significant impact on the development of new lethal antibiotics and for the treatment of recalcitrant and drug-resistant pathogens.

Gastrointestinal disease is the most common cause of mortality in dairy calves. Septicemia is an important sequela of diarrhea, and the possibility of bacteremia is the primary justification for empirical antimicrobial therapy. Prior reports estimate that approximately onethird of diarrheic calves are bacteremic; however, those estimates may not be representative of routine cases in heifer calves on commercial dairy operations early in the course of disease. We hypothesized that the prevalence of bacteremia in calves with diarrhea and systemic signs of illness is less than prior estimates (~31%), and that clinical signs or hematological values would be associated with the presence or absence of bacteremia. Female calves less than 21 d of age with and without diarrhea were enrolled from 2 commercial dairy farms over a 10-wk period. Diarrheic calves were enrolled if they were newly diagnosed, had loose to watery stool, had either dehydration (assessed by skin tent and eye position) or depression (assessed by suckle reflex and standing ability), and had no prior antimicrobial treatments. Complete health assessments were conducted at 0, 7, and 14 d following enrollment. An aseptic jugular venous sample was collected and cultured using aerobic and anaerobic methods, and bacterial species were identified using mass spectrometry. Poisson regression models were used to identify associations with bacteremia and compute adjusted prevalence ratios. The prevalence of bacteremia in diarrheic and healthy calves was 9.26% (10/108, 95% confidence interval: 4.5-16%) and 14.8% (4/27, 95% confidence interval: 1.4-28.2%), respectively. Among calves with diarrhea, those with a fever (>39.7°C) or depression were 4.8 and 6.5 times more likely, respectively, to have bacteremia. Only 1 of 47 calves (2%) without signs of depression was bacteremic. The prevalence of bacteremia in diar-rheic calves with signs of systemic illness (depression or dehydration) was significantly lower than previous estimates, and bacteremia was rare among calves without observed depression. Antimicrobial therapy targeting bacteremia is not currently justified in routine cases of diarrhea in preweaning calves without signs of depression. These results suggest a substantial opportunity for more targeted antimicrobial therapy to improve antimicrobial stewardship.

Two unrelated bovine beef calves, aged 2 mo and 3 mo, were presented to The Ohio State University Veterinary Medical Center because of scrotal swelling and abdominal distension. On postmortem examination, there was abundant peritoneal fluid and numerous small friable masses covering all peritoneal surfaces and extending into the scrotum via the tunica vaginalis, with no identifiable primary neoplasm. Based on light microscopy, differential diagnoses included malignant mesothelioma and anaplastic carcinoma. Immunohistochemically, the neoplasms labeled positive for cytokeratin, and negative for vimentin and calretinin. Neoplastic cells contained periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules, and lacked Alcian blue-positive, hyaluronidase-negative cytoplasmic vacuoles. Ultrastructurally, the cells had features of carcinoma, including secretory granules, and lacked typical features of mesothelioma, such as long slender microvilli. Our final diagnosis was carcinoma in both calves, despite the equivocal gross and light microscopic findings. We propose that a presumptive diagnosis of peritoneal mesothelioma in bovine calves should be avoided without corroboration by a combination of histology, histochemistry, immunohistochemistry, and, if possible, electron microscopy.