A Longitudinal Assessment of Self-directed Learning Readiness and Development in Medical Students.

OBJECTIVES: Self-directed learning (SDL) competency is important for physicians to stay abreast of advances in their field and to provide the best available evidence-based care to their patients. Therefore, an essential responsibility of medical educators is to ensure the development of SDL skills in their students. The first objective of this study was to investigate longitudinally the degree to which medical students were ready to engage in SDL. The second objective was to examine students' perceptions of their SDL development throughout training. METHODS: A 2-part study of preclinical and clinical medical students was carried out at a midwestern U.S. university. In Study A, a longitudinal assessment of preclinical medical students' readiness to engage in SDL was conducted by administering an SDL readiness survey (SDLRS). In Study B, third- and fourth-year medical students were asked to reflect on their SDL development, in addition to completing the SDLRS. RESULTS: After validating the Hendry and Ginns version of the SDLRS in preclinical medical students during Study A, we found that 3 of the 4 subscales remained constant over the 3 iterations of the survey while the self-determination subscale increased significantly between the first and third iteration of the survey. In Study B, an analysis of the clinical medical students' comments indicated a perceived increase in their SDL abilities and a growing appreciation of SDL. However, the SDLRS scores of clinical students did not differ from the results observed in preclinical students in Study A. CONCLUSIONS: The results of the SDLRS indicated that the experience of students in our medical school has a positive influence on self-determination by the end of the preclinical years. Furthermore, analysis of the reflections of clinical students indicated ongoing development of SDL skills throughout their medical school training that were influenced by a wide range of experiences.

Pharmacist-social worker interprofessional relations and education in mental health: a scoping review.

Background: One in eight patients is affected by a mental health condition, and interprofessional mental health teams collaborate to improve patient care. While pharmacists and social workers are recognized as mental health team members, there is a lack of literature describing interprofessional relations and education between these professions, especially as it pertains to mental health. The purpose of this review was to identify and characterize reports describing pharmacist-social worker interprofessional relations and education within mental health. Methodology: To address this knowledge gap, this scoping review was conducted to collect and characterize reports published between January 1, 1960 and August 18, 2023 describing pharmacist-social worker interprofessional relations and education within the field of mental health. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines were followed. Ovid MEDLINE, CINAHL, and Social Work Abstracts were searched using keywords "pharmacy student," "pharmacist," "social work student," "social worker," and "social work." Reports were included if they were published in English and interprofessional relations or education occurred directly between (student) pharmacists and social workers. Results: Three hundred twenty records were identified and three records were included: one cross sectional study, one qualitative educational project, and one case report. Each record suggested positive patient and/or educational outcomes developing from pharmacist-social worker interprofessional relations and education. In clinical practice, pharmacist-social work teams identified mental health risk factors, reduced 30-day readmissions, and improved post-discharge telehealth care. In the classroom, a social worker improved pharmacy students' confidence assessing patient suicidal ideations. Conclusions: This scoping review identified needs and areas for future research: pharmacist interprofessional education with Master of Social Work and Doctor of Social Work degree students, transitional care and mental health outcome measure reporting using evidence-based outcomes, and development of scholarly teaching projects utilizing higher-level educational frameworks beyond learner reactions.

The Impact of COVID-19 Fear on Mental Health of Community Behavioral Health Providers.

OBJECTIVE: The COVID-19 pandemic has impacted communities worldwide. Behavioral health providers are at the forefront providing services and are thus vulnerable to psychological sequalae. This study hypothesizes that the fear of COVID-19 predicts depression and anxiety among these providers. METHODS: A questionnaire was delivered to community behavioral health providers to assess fear of COVID-19 using the Fear of COVID-19 Scale (FCV-19S). Anxiety and depression were assessed using Generalized Anxiety Disorder (GAD-2) scale and Patient Health Questionnaire (PHQ-2). Demographic data were analyzed using descriptive statistics, and the relationship between explanatory variables and outcomes was assessed using univariate generalized linear models and 1-way analysis of variance (ANOVA). RESULTS: FCV-19S scores were significantly higher among persons who smoked (z = 2.4, P < 0.05) or had a predisposing health condition. The multivariate models showed significant association with fear of COVID-19 and having a predisposing health condition, belonging to an ethnic minority group, not been diagnosed positive, and having a high total anxiety score. CONCLUSIONS: The study indicated that 50% of the behavioral health providers screened had poor mental health owing to multiple factors identified. Hence, it is essential to strengthen their support to better mitigate situations contributing to fear.

Fear of COVID-19 among nonsmokers and smokers/former smokers: Implications for health promotion practice.

INTRODUCTION: Fear of COVID-19 may differ for individuals with compromised health and those with unhealthy behaviors, placing them at greater risk. Based on previous analysis of academic medical center faculty and staff, the authors predicted that workers who were smokers/previous smokers would express the greater fear of COVID-19 relative to nonsmokers. METHODS: The present study used the Fear of COVID-19 Scale to assess fear among nonsmokers (n = 1,489) and smokers/previous smokers (n = 272) from a larger population of academic medical center members (N = 1,761). This study assessed nonsmokers' and smokers/previous smokers' demographic and background variables on Fear of COVID-19 scores. RESULTS: In this academic community, smokers/previous smokers had higher fear of COVID-19 scores than did nonsmokers (p < 0.05). Smokers/previous smokers differed from nonsmokers on three Fear of COVID-19 scale items (most afraid of COVID-19, fear of losing life, and physiological fear of COVID-19). DISCUSSION/CONCLUSIONS: These results provide a better understanding of how fear of COVID-19 can differ based on one's smoking status. These findings inform public health smoking cessation efforts aimed at reducing morbidity and mortality, both in response and secondary to COVID-19 exposure.

The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception.

Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophin-releasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNST(AL)). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNST(AL). Mechanical sensitivity was quantified using electronic von Frey filaments, and colonic nociception was measured by quantifying a visceromotor response to graded colorectal distension. In situ hybridization was used to determine mRNA levels for CRF, CRF(1), and CRF(2) receptors in the BNST(AL). In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNST(AL) to administer a CRF(1) receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNST(AL), exhibited increased expression of CRF mRNA and increased CRF(1)-to-CRF(2) receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNST(AL) inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF(1) receptor-dependent mechanism in the BNST(AL). The CeA through a descending pathway involving the BNST(AL) plays a pivotal role in somatic and colonic nociception.

Fear of COVID-19 among nonsmokers and smokers/former smokers: Implications for health promotion practice.

INTRODUCTION: Fear of COVID-19 may differ for individuals with compromised health and those with unhealthy behaviors, placing them at greater risk. Based on previous analysis of academic medical center faculty and staff, the authors predicted that workers who were smokers/previous smokers would express the greater fear of COVID-19 relative to nonsmokers. METHODS: The present study used the Fear of COVID-19 Scale to assess fear among nonsmokers (n = 1,489) and smokers/previous smokers (n = 272) from a larger population of academic medical center members (N = 1,761). This study assessed nonsmokers' and smokers/previous smokers' demographic and background variables on Fear of COVID-19 scores. RESULTS: In this academic community, smokers/previous smokers had higher fear of COVID-19 scores than did nonsmokers (p < 0.05). Smokers/previous smokers differed from nonsmokers on three Fear of COVID-19 scale items (most afraid of COVID-19, fear of losing life, and physiological fear of COVID-19). DISCUSSION/CONCLUSIONS: These results provide a better understanding of how fear of COVID-19 can differ based on one's smoking status. These findings inform public health smoking cessation efforts aimed at reducing morbidity and mortality, both in response and secondary to COVID-19 exposure.

Sex Differences between Medical Students in the Assessment of the Fear of COVID-19.

Background: Differing expressions of the fear of COVID-19 between men and women can potentially increase both immediate and long-term physical health risks. We predicted that women students would express greater fear of COVID-19. Methods: We used an Internet-delivered Fear of COVID-19 Scale (FCV-19S) to assess fear among men (n = 100) and women (n = 272) from a larger population of academic medical center members (n = 1761). Sex differences in emotional and physical symptoms were assessed as subcategories within fear scores. Results: Women reported greater fear of COVID-19 than men (p < 0.001). Women reported greater emotional fear (p < 0.001) on specific scale items (thinking of COVID-19, watching news stories about COVID-19, and losing sleep due to fear of contracting COVID-19). Discussion/Conclusions: These results provide a better understanding of how fear of COVID-19 can differ based on sex and how that fear may be expressed differently through emotional and physical symptoms. This information will inform academic health centers of COVID-19 prevention and management policies that may include a gender-specific focus.

Efficacy of vitrectomy in improving the outcome of Bacillus cereus endophthalmitis.

PURPOSE: To evaluate the efficacy of vitrectomy with vancomycin for the treatment of experimental Bacillus cereus endophthalmitis. METHODS: Endophthalmitis was initiated in rabbits via intravitreal injection of 100 colony-forming unit B. cereus. Treatment groups included 25-gauge transconjunctival sutureless vitrectomy with intravitreal vancomycin (1 mg) or vancomycin alone. Groups were treated at 4, 5, or 6 hours after infection. At 48 hours (for 4-hour and 5-hour groups) or 36 hours (for the 6-hour group) after infection, eyes were analyzed by electroretinography, histology, and inflammatory cell counts. RESULTS: Treatment with vitrectomy/vancomycin at 4 hours resulted in significantly greater retinal function compared with that of vancomycin alone. Intraocular inflammation after treatment at 4 hours was minimal for both the treatment groups. Treatment with vitrectomy/vancomycin or vancomycin alone at 5 hours or 6 hours after infection resulted in similar levels of retinal function loss (i.e., >90%) and significant intraocular inflammation. CONCLUSION: These results demonstrate that vitrectomy may be of therapeutic benefit in the treatment of B. cereus endophthalmitis but only during the early stages of infection.

Assessing fear of COVID-19 at an academic medical center.

PURPOSE: This study measured the degree of COVID-19-related fear among academic medical center employees, identified subsections with high COVID-19 fear, and validated the Fear of COVID-19 Scale with medical professionals in the United States. METHODS: This study is a cross-sectional, internet-based survey delivered by Qualtrics. The survey was conducted at the Oklahoma University Health Sciences Center between May 21 and June 18, 2020. The medical center is composed of seven healthcare colleges, child and adult hospitals, a Veterans Hospital, and outpatient services clinics across the Oklahoma city area. Faculty, staff, and students (N = 1,761) from the Oklahoma University Health Sciences Center completed the survey. RESULTS: COVID-19 fear is highest among nonclinical employees, smokers, and those with pre-existing conditions. Males and females, both clinicians and nonclinicians, appear to express their COVID-19 fears differently. Employees worried most about their families contracting the virus. The Fear of COVID-19 Scale is a valid and reliable assessment instrument among US healthcare workers. Responses were compared based on pre-existing medical condition(s), patient care or nonpatient care, sex, and occupational specialization. Analyses reveal a strong Cronbach's α measure of internal consistency (α = 0.87). Significant differences were observed among employees with a nonclinical emphasis (p = 0.02), with a predisposing medical health condition (p < 0.001), and with a nonacademic occupational specialization (p < 0.01), and by sex (p < 0.001). CONCLUSIONS AND DISCUSSION: COVID-19 fear significantly impacts academic medical center employees. Medical centers should address both healthcare and nonhealthcare workers' COVID-19-related fears. It is important to recognize that men and women may have different types of fears and express them differently, necessitating a gender-specific approach to managing COVID-19 fears. Employees with pre-existing conditions or who have vulnerable family members require additional support to remain fully functional and on the job.

The aging colon: the role of enteric neurodegeneration in constipation.

Constipation is a common problem in the elderly, and abnormalities in the neural innervation of the colon play a significant role in abnormalities in colonic motility leading to delayed colonic transit. The scope of this review encompasses the latest advances to enhance our understanding of the aging colon with emphasis on enteric neurodegeneration, considered a likely cause for the development of constipation in the aging gut in animal models. Neural innervation of the colon and the effects of aging on intrinsic and extrinsic nerves innervating the colonic smooth muscle is discussed. Evidence supporting the concept that neurologic disorders, such as Parkinson's disease, not only affect the brain but also cause neurodegeneration within the enteric nervous system leading to colonic dysmotility is presented. Further research is needed to investigate the influence of aging on the gastrointestinal tract and to develop novel approaches to therapy directed at protecting the enteric nervous system from neurodegeneration.

Mentee Assessment of Mentoring Competencies at an Academic Health Sciences Center.

The Oklahoma Center for Mentoring Excellence (OCME) initiated faculty workshops to enhance their mentoring skills and establish an intercampus network for faculty specializing in clinical and biomedical sciences. The initial importance of mentoring competencies based on early career faculty members' perception and experience had not yet been determined. The Mentoring Competency Assessment validated by Fleming et al. (2013b) was used to rate the perceived importance of competencies and assess senior faculty members' competencies using a seven-point range, Likert-type response scale. Responses were analyzed by presence or absence of a mentor, previous formal mentor training, sex, and health science discipline. Junior faculty (n = 144) rated each competency as important or greater across all categories. A majority (70%) reported not having a current mentor. Junior faculty with current mentors rated senior faculty competencies higher than junior faculty without; participation in formal mentor training as well as a clinical faculty appointment were independently associated with higher assessment scores. This study identifies specific population characteristics that may serve to enhance the effectiveness of OCME workshops and demonstrates that junior faculty identify mentoring as significantly important in their academic career success in a research and clinical health setting.

Toward improving therapeutic regimens for Bacillus endophthalmitis.

PURPOSE: Bacillus cereus causes the most virulent and refractory form of endophthalmitis. The authors analyzed the effectiveness of early treatment with vancomycin or gatifloxacin, with or without dexamethasone, for experimental B. cereus endophthalmitis. METHODS: Rabbit eyes were injected intravitreally with 100 colony-forming units of B. cereus. At 2, 4, or 6 hours after infection, eyes were injected intravitreally with 0.1 mL gatifloxacin (0.3%), vancomycin (1.0%), either antibiotic plus dexamethasone, dexamethasone alone (1.0%), or PBS. Eyes were analyzed by electroretinography, bacterial quantitation, and antibiotic penetration analysis. Drug toxicity toward Müller cells, retinal pigment epithelium, and cones was also analyzed. RESULTS: Eyes treated at 2 hours with vancomycin or gatifloxacin, with or without dexamethasone, maintained higher ERG amplitudes than the dexamethasone alone and PBS control groups. Eyes treated with antibiotic plus dexamethasone at 6 hours had reduced retinal function compared to antibiotic treatment alone. With the exception of vancomycin with or without dexamethasone at 6 hours, all antibiotic treatments sterilized eyes. Only gatifloxacin reached aqueous concentrations greater than the minimal inhibitory concentration for B. cereus when measured at 8 hours. Neither gatifloxacin nor vancomycin was toxic to retinal cells in vitro. CONCLUSIONS: Early intravitreal injection of vancomycin or gatifloxacin improved the therapeutic outcome of B. cereus endophthalmitis. The addition of dexamethasone to antibiotic treatment did not provide a therapeutic benefit over antibiotics alone and appeared to reduce the antibiotic efficacy of vancomycin 6 hours after infection. In this model, delay in treatment past 6 hours significantly reduced the potential for salvaging useful vision.

Bacterial endophthalmitis: therapeutic challenges and host-pathogen interactions.

Endophthalmitis is an infection of the posterior segment of the eye that frequently results in loss of vision. This devastating result occurs despite prompt and often aggressive therapeutic and surgical intervention. Over the past decade, research has centered on determining the bacterial and host factors involved in this potentially blinding disease. The initial focus on the bacterial factors responsible for intraocular virulence has recently expanded into analysis the inflammatory response to infection, including the molecular and cellular interactions between the pathogen and host. This review discusses the epidemiology and therapeutic challenges posed by endophthalmitis, as well as recent findings from the analysis of interactions between the host and pathogen. Based on these findings, a model for the pathogenesis of endophthalmitis is presented. A more comprehensive understanding of the molecular and cellular interactions taking place between pathogen and host during endophthalmitis will expose possible therapeutic targets designed to arrest the infection and prevent vision loss.

Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis.

Blood-Retinal Barrier Compromise and Endogenous Staphylococcus aureus Endophthalmitis.

PURPOSE: To test the hypothesis that blood-retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis. METHODS: To compromise the blood-retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus-induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti-ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays. RESULTS: We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 × 103 ± 1.78 × 10² cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 × 10² ± 7.09 × 10² cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 × 10² ± 2.49 × 10² cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 × 10² ± 1.08 × 10³ cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier. CONCLUSIONS: Taken together, these results indicated that S. aureus is capable of inducing blood-retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals.

The diabetic ocular environment facilitates the development of endogenous bacterial endophthalmitis.

PURPOSE: We tested the hypothesis that changes in the diabetic ocular environment facilitate the development of endogenous bacterial endophthalmitis (EBE). METHODS: C57BL/6J mice were rendered diabetic with streptozotocin (STZ) for 1, 3, or 5 months' duration. Diabetic and age-matched nondiabetic mice were tail vein-injected with 10(8) CFU of Klebsiella pneumoniae, a common cause of EBE in diabetics. After either 2 or 4 days postinfection, the EBE incidence was assessed by electroretinography, histology, bacterial counts, and myeloperoxidase ELISAs. Blood-retinal barrier (BRB) permeability in uninfected diabetic mice also was determined. RESULTS: No cases of EBE were observed among the 1-month diabetic group. Extending the time from diabetes induction to 3 months resulted in a 23.8% EBE incidence after 2 days, and a 22% incidence after 4 days. The incidence of EBE increased to 27% in the 5-month diabetic group. Infected eyes had an average 8.01 × 10(2) and 6.19 × 10(4) CFU/eye for the 3- and 5-month diabetic groups, respectively. There was no significant difference in BRB permeability between control and 1-month uninfected diabetic mice. However, 3- and 5-month diabetic mice had significantly greater BRB permeability than control mice. These results suggested that increasing the time from STZ diabetes induction to 3 and 5 months resulted in an ocular environment more conducive to the development of EBE. CONCLUSIONS: These results demonstrated a correlation between an increase in BRB permeability and an increase in EBE incidence, supporting the hypothesis that diabetic ocular changes contribute to the development of EBE.

Diabetes reduces autophosphorylation of retinal insulin receptor and increases protein-tyrosine phosphatase-1B activity.

PURPOSE: Protein-tyrosine phosphatase-1B (PTP1B) has been implicated in the negative regulation of insulin signaling. The expression, activity, and functional role of PTP1B in the retina are unknown. In this study, the authors examined the relationship between the retinal insulin receptor (IR) and PTP1B in normal and diabetic mouse retinas. METHODS: IR and PTP1B localization was examined by immunohistochemistry. The activation of IR was analyzed using specific antibodies against phosphotyrosine. PTP1B activity was determined in anti-PTP1B immunoprecipitates. Glutathione-S-transferase fusion proteins containing wild-type and catalytically inactive mutant PTP1B was used to study the interaction between IR and PTP1B. Anti-IR immunoprecipitates and the cytoplasmic domain of purified IR were incubated in the presence of ATP, and the autophosphorylation of IR with antiphosphotyrosine antibody was analyzed. RESULTS: Immunohistochemical analysis of PTP1B shows that it is predominantly expressed in nonphotoreceptor layers of the retina, though it is clearly expressed in the inner segments of the rod photoreceptors. The IR is predominately expressed in rod inner segments. Biochemical analysis of rod outer segments indicates the presence of IR and PTP1B. Retinal IR exhibits a high level of basal autophosphorylation, and this autophosphorylation is reduced in diabetic mouse retinas. In vitro, PTP1B is able to dephosphorylate the autophosphorylated IR. Substrate mutant-trap results indicate a stable interaction between IR and PTP1B. Further, PTP1B activity was increased in diabetic mouse retinas. CONCLUSIONS: These studies indicate that diabetes reduces the autophosphorylation of retinal IR and increased PTP1B activity. Further, PTP1B regulates the state of IR phosphorylation in the retina.

Rate of bacterial eradication by ophthalmic solutions of fourth-generation fluoroquinolones.

INTRODUCTION: Antibacterial activity of ophthalmic fourth-generation fluoroquinolones has traditionally been evaluated by comparing only their active ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of fourth-generation fluoroquinolones differ in terms of the inclusion of preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar; Allergan, Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin ophthalmic solution 0.5% (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX, USA) is preservative-free. Recent studies have demonstrated that the presence of BAK dramatically affects the antibacterial activity of the ophthalmic formulation of gatifloxacin. This study was designed to compare the kill rates of ophthalmic solutions of fourth-generation fluoroquinolones against isolates of common ocular bacterial pathogens. METHODS: Approximately 5.6 log(10) colony-forming units (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1), Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified at specific time points up to 60 minutes. RESULTS: Gatifloxacin 0.3% completely eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus isolates in 15 minutes, and the other S. aureus isolate in 60 minutes. Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4 log(10) CFU/mL. CONCLUSIONS: The ophthalmic solution of gatifloxacin 0.3% eradicated bacteria that frequently cause postoperative ocular infections substantially faster than did the ophthalmic solution of moxifloxacin 0.5%.

Hypermucoviscosity as a virulence factor in experimental Klebsiella pneumoniae endophthalmitis.

PURPOSE: Klebsiella pneumoniae is a common cause of endogenous bacterial endophthalmitis, a disease that frequently results in a poor visual outcome. Hypermucoviscosity has been identified as a virulence factor among clinical bacteremia isolates of K. pneumoniae. In this study, an experimental murine model of K. pneumoniae endophthalmitis was established, and the role of hypermucoviscosity in its pathogenesis was analyzed. METHODS: C57BL/6J mice were intravitreously injected with 100 CFU of hypermucoviscous (HMV+) or nonhypermucoviscous (HMV-) K. pneumoniae. Intraocular bacterial growth, retinal function, gross pathology, and inflammatory responses were monitored every 3 hours until the eyes lost significant (>90%) retinal function, or the infection appeared to clear. RESULTS: The HMV+ strain grew logarithmically in eyes until approximately 15 hours postinfection (PI), reaching a stationary phase of growth at approximately 8.0 log(10) CFU/eye. The HMV- strain grew logarithmically to approximately 7.6 log(10) by 18 hours, but bacterial count declined to approximately 6.4 log(10) CFU/eye by 21 hours PI. Eyes infected with the HMV+ strain retained approximately 35% a-wave and <10% b-wave function by 18 hours PI. These eyes also had a cumulative clinical score of 14+ by 18 hours and underwent phthisis between 21 and 24 hours. Eyes infected with the HMV- strain had a cumulative clinical score of <6 and retained >60% a-wave and >50% b-wave function throughout 21 hours. Five of 7 eyes had <100 CFU HMV- K. pneumoniae at 27 hours PI. CONCLUSIONS: The findings demonstrate the site-threatening consequences of K. pneumoniae endophthalmitis and the importance of the hypermucoviscosity phenotype in the pathogenesis of experimental K. pneumoniae endophthalmitis.