Ceftriaxone 1 g Versus 2 g Daily for the Treatment of Enterobacterales Bacteremia: A Retrospective Cohort Study.

Background: Ceftriaxone is a commonly used antibiotic for the treatment of susceptible Enterobacterales infections. There is currently limited clinical data on the optimal dose of ceftriaxone for Enterobacterales bacteremia. Objectives: To evaluate the rate of clinical failure of ceftriaxone 1 g versus 2 g daily in patients with Enterobacterales bacteremia. Methods: This was a retrospective cohort study of patients admitted to any of the 3 New York University Hospitals: Long Island, Tisch, or Brooklyn, with ceftriaxone-susceptible Enterobacterales bacteremia, receiving ceftriaxone 1 or 2 g daily from October 2019 to September 2020. The primary outcome was 90-day rate of clinical failure. Clinical failure was defined as escalation of therapy, relapse of infection, or all-cause mortality. Results: A total of 124 patients, 58% in the 1-g group and 42% in the 2-g group, were included. There was no statistically significant difference found in the primary outcome. The 90-day rate of clinical failure was 16.7% versus 9.6%, P = 0.260. There were no statistically significant secondary outcomes, although infection relapse rates at 90 days were numerically greater in the 1-g group (11.1% vs 1.9%, P = 0.078). Hypoalbuminemia was the only variable associated with an increased risk of clinical failure (odds ratio = 4.03; 95% confidence interval [CI] = 1.12-14.50, P = 0.033). Conclusion: In our exploratory findings, there was no statistically significant difference with the 90-day rate of clinical failure between ceftriaxone 1 g versus 2 g daily, although there was a numeric trend toward an increased rate of infection relapse within the 1-g group. Hypoalbuminemia was associated with an increased risk of clinical failure. Prospective studies are warranted to confirm these findings.

The relationship between education levels, lifestyle, and religion regarding the prevalence of myopia in Israel.

BACKGROUND: The ultra-Orthodox Jewish community has a unique lifestyle including minimal outdoor activity and intense, prolonged nearby work, beginning at a very young age. Their prevalence of myopia is extremely high. This paper provides a unique insight into the attitudes of this community towards myopia. METHODS: Ultra-Orthodox Jewish parents of children who came to the pediatric ophthalmology clinic in one tertiary care and two community centers in ultra-Orthodox-oriented cities were given a questionnaire. Demographic information, along with myopia prevalence in the family, was gathered. In addition, their attitudes and common knowledge regarding myopia were investigated. RESULTS: 161 questioners were collected, mostly completed by mothers (n = 110, 68%). The average number of children per family was 6 (range 1-16). In 148 families (92%) at least one of the parents has myopia. The average parent refraction was - 4.5 diopters (range - 0.5 to 15 diopters). Out of 935 children, 410 (44%) wore glasses. Twelve parents (7%) believe that myopia is a disease and 94 (58%) reported that they are concerned because their child wears glasses. Twenty-four (15%) believe that glasses are a sign of a high education level. Regarding treating myopia progression, 144 (89%) think that myopia progression should be treated, but only 36 (22%) are aware of the available treatments for it. CONCLUSION: This study examines an insular community with a very high incidence of myopia. In this community most parents think that myopia progression should be treated but most of them are unaware of the currently available treatments.

Outcomes of COVID-19 Patients Hospitalized at Acute Care Services: Real-World Experience in the New York Metropolitan Area During the Early Pandemic Before Initiation of Clinical Trials.

As New York became the epicenter of the COVID-19 pandemic early on, clinicians were challenged to provide optimal medical and pharmaceutical care, despite the paucity of supporting literature and guidance. We sought to describe prescribing patterns and outcomes of physician response to the urgent need to treat COVID-19 patients before initiation of randomized clinical trials. METHODS: This was a retrospective cohort study of adult patients with COVID-19 initially admitted to acute care services during March 2020. Critically ill patients requiring intensive care unit level of care on admission were excluded. RESULTS: A total of 639 consecutive patients (supportive care, n = 247; treatment n = 392) were included in the analysis. Overall, the 28-day mortality rate was 12.2%. The mortality was 8.7% higher in the treatment group (15.6% vs 6.9% in the supportive care group, P < 0.001). Treatment was not protective against progression to severe disease (18.4% vs 3.6% with supportive care, P < 0.0001). Time to defervescence, duration of oxygen support, and hospital and intensive care unit (ICU) length of stay were also higher in the treatment group. In multivariate analysis, 60 years or older, presence of severe disease, and need for ICU admission were identified as independent predictors of 28-day mortality. There were 41 (10.5%) adverse event in the treatment group, with the majority being QT prolongation and gastrointestinal effects. CONCLUSIONS: In this cohort of hospitalized patients admitted to acute care services, treatment with hydroxychloroquine, lopinavir/ritonavir or both could not be shown to improve mortality, progression to severe disease, or clinical response.

Intracameral cefuroxime and the incidence of post-cataract endophthalmitis: an Israeli experience.

PURPOSE: The European Society of Cataract & Refractive Surgeons (ESCRS) study reported a decrease in endophthalmitis rates from 0.34 % to 0.08 % with the use of intracameral cefuroxime. The purpose of this study was to compare the endophthalmitis rates before and after the introduction of intracameral cefuroxime (ICC) routinely at the end of cataract surgery. METHODS: A retrospective consecutive cohort study. We compared the rates of endophthalmitis between the years 2000-2006, and the years 2007-2014, after the pivotal publication of the ESCRS. Data collected included age, gender, culture results, initial and final visual acuity, and complications. Only patients that presented with endophthalmitis following cataract surgery performed at the two centers were included. RESULTS: Twenty-two cases of endophthalmitis occurred between the years 2000 and 2006, out of 26,663 cataract operations performed at the two centers, a rate of 0.083 %. Ten cases occurred between the years 2007 and 2014 out of 29,431 cataract operations, a rate of 0.034 %. The difference was statistically significant (p = 0.03) CONCLUSIONS: The introduction of prophylactic use of intracameral cefuroxime was associated with a significant reduction in post-operative endophthalmitis rates in our centers. We strongly recommend adoption of this routine by for all cataract operations except when contraindicated.

Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

Long-term retinal changes after strabismus surgery, suspected signs of past scleral perforations.

Purpose: Scleral perforation during strabismus surgery is considered a rare complication that usually results in no significant consequences. The true rate of such occurrences is difficult to evaluate due to the young age of most patients and the occult nature of most events. This study aimed to evaluate long-term retinal changes under the suture areas in patients post-strabismus surgery as presumed signs indicating past undiscovered scleral perforations. Methods: The study population consisted of patients with a follow-up of at least 10 years post-strabismus surgery at the [redacted for review] Eye Institute and with no known retinal conditions as well as with wide fundus visibility. We performed slit-lamp retinal periphery examinations in search of retinal scars or changes at the suture sites. Results: Seventy-one eyes from 43 patients were examined. The mean age (±standard deviation [SD]) at the time of examination was 27 years (±14), and the mean number of strabismus surgeries per patient was 1.8. Three of the examined eyes showed retinal changes at the suture sites, yielding an overall incidence rate of suspected perforation/penetration of 4.2% per eye and 3.6% per strabismus surgery. These three patients were all asymptomatic. Conclusion: Scleral perforations during strabismus surgeries could remain unnoticed since a comprehensive exam of the retinal periphery is challenging in young children, especially during the postoperative period. While retinal changes caused by inadvertent scleral perforations appear to have no clinical sequelae in a time frame of 10 years, such changes should be noted for future fundoscopic examinations.

The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

BACKGROUND/OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.

Risk factors associated with abandonment of care in retinoblastoma: analysis of 692 patients from 10 countries.

BACKGROUND: Rates of care abandonment for retinoblastoma (RB) demonstrate significant geographical variation; however, other variables that place a patient at risk of abandoning care remain unclear. This study aims to identify the risk factors for care abandonment across a multinational set of patients. METHODS: A prospective, observational study of 692 patients from 11 RB centres in 10 countries was conducted from 1 January 2019 to 31 December 2019. Multivariate logistic regression was used to identify risk factors associated with higher rates of care abandonment. RESULTS: Logistic regression showed a higher risk of abandoning care based on country (high-risk countries include Bangladesh (OR=18.1), Pakistan (OR=45.5) and Peru (OR=9.23), p<0.001), female sex (OR=2.39, p=0.013) and advanced clinical stage (OR=4.22, p<0.001). Enucleation as primary treatment was not associated with a higher risk of care abandonment (OR=0.59, p=0.206). CONCLUSION: Country, advanced disease and female sex were all associated with higher rates of abandonment. In this analysis, enucleation as the primary treatment was not associated with abandonment. Further research investigating cultural barriers can enable the building of targeted retention strategies unique to each country.

Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries.

OBJECTIVE: To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. METHODS: A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. RESULTS: For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). CONCLUSIONS: No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.

Lag Time between Onset of First Symptom and Treatment of Retinoblastoma: An International Collaborative Study of 692 Patients from 10 Countries.

BACKGROUND: The relationship between lag time and outcomes in retinoblastoma (RB) is unclear. In this study, we aimed to study the effect of lag time between onset of symptoms and diagnosis of retinoblastoma (RB) in countries based on their national-income and analyse its effect on the outcomes. METHODS: We performed a prospective study of 692 patients from 11 RB centres in 10 countries from 1 January 2019 to 31 December 2019. RESULTS: The following factors were significantly different among different countries based on national-income level: age at diagnosis of RB (p = 0.001), distance from home to nearest primary healthcare centre (p = 0.03) and mean lag time between detection of first symptom to visit to RB treatment centre (p = 0.0007). After adjusting for country income, increased lag time between onset of symptoms and diagnosis of RB was associated with higher chances of an advanced tumour at presentation (p < 0.001), higher chances of high-risk histopathology features (p = 0.003), regional lymph node metastasis (p < 0.001), systemic metastasis (p < 0.001) and death (p < 0.001). CONCLUSIONS: There is a significant difference in the lag time between onset of signs and symptoms and referral to an RB treatment centre among countries based on national income resulting in significant differences in the presenting features and clinical outcomes.

The Effects of Breastfeeding on Retinoblastoma Development: Results from an International Multicenter Retinoblastoma Survey.

The protective effects of breastfeeding on various childhood malignancies have been established but an association has not yet been determined for retinoblastoma (RB). We aimed to further investigate the role of breastfeeding in the severity of nonhereditary RB development, assessing relationship to (1) age at diagnosis, (2) ocular prognosis, measured by International Intraocular RB Classification (IIRC) or Intraocular Classification of RB (ICRB) group and success of eye salvage, and (3) extraocular involvement. Analyses were performed on a global dataset subgroup of 344 RB patients whose legal guardian(s) consented to answer a neonatal questionnaire. Patients with undetermined or mixed feeding history, family history of RB, or sporadic bilateral RB were excluded. There was no statistically significant difference between breastfed and formula-fed groups in (1) age at diagnosis (p = 0.20), (2) ocular prognosis measures of IIRC/ICRB group (p = 0.62) and success of eye salvage (p = 0.16), or (3) extraocular involvement shown by International Retinoblastoma Staging System (IRSS) at presentation (p = 0.74), lymph node involvement (p = 0.20), and distant metastases (p = 0.37). This study suggests that breastfeeding neither impacts the sporadic development nor is associated with a decrease in the severity of nonhereditary RB as measured by age at diagnosis, stage of disease, ocular prognosis, and extraocular spread. A further exploration into the impact of diet on children who develop RB is warranted.

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

The effect of probiotics on the incidence of Clostridioides difficile: Retrospective cohort analysis.

BACKGROUND: Conflicting evidence exists regarding probiotics and the incidence of Clostridioides difficile infection (CDI). This study evaluates whether probiotics are efficacious for CDI prophylaxis in patients receiving antibiotics. METHODS: A retrospective cohort analysis of patients admitted to NYU Winthrop Hospital who received at least 1 dose of antibiotics considered high risk of inducing CDI. Patients were grouped according to probiotic use; association between probiotic use and incident CDI was examined. A model for incident CDI adjusting for known CDI risk factors was estimated. RESULTS: Of 3,267 patients, 4.6% had CDI within 12 weeks of antibiotics initiation. A total of 5.1% received probiotics within 24 hours of initiation, and 6.6% initiated probiotics during the 12-week follow-up. Of those taking probiotics within 24 hours of antibiotics, 9.6% had CDI, and of those not taking probiotics 4.2% had CDI (relative risk, 2.3; 95% confidence interval, 1.4, 3.7). In time-dependent Cox models accounting for probiotic initiation and adjusting for potential confounders, a positive association between probiotics and CDI remained significant (hazard ratio, 2.7; P < .001). DISCUSSION: Patients who received antibiotics with concurrent probiotics were more likely to have an incident of CDI compared with those who did not receive probiotics. Additional risk factors were histamine 2 receptor antagonists, proton pump inhibitors, and administration of multiple antibiotics simultaneously. CONCLUSIONS: The present study, because of its large population and inclusion of multiple variables playing a role in CDI, serves as a valuable resource when considering efficacy of probiotics as CDI prophylaxis.

Lack of Pharmacokinetic Basis of Weight-Based Dosing and Intra-Operative Re-Dosing with Cefazolin Surgical Prophylaxis in Obese Patients: Implications for Antibiotic Stewardship.

Traditionally, there have been uniform antibiotic dosing guidelines for prophylaxis for clean-clean-contaminated surgery in both non-obese and obese adults. All other factors predisposing to surgical site infections (SSIs) being equal, over time, the preferred drug is cefazolin. The usual dose, given immediately pre-procedure, has been 1 g intravenously (IV) in non-penicillin-allergic patients, which has been highly effective, Recently, it has become common practice to use high-dose cefazolin; i.e., 3 g IV, in obese patients. This article reviews the literature on high-dose cefazolin prophylactic regimens in the obese from a pharmacokinetic (PK) point of view. There are no comparative studies to support this approach, which is based largely on the theory "more must be better." Weight-based dosing of cefazolin in the obese is flawed, because it does not take into account PK factors, which are critical in the obese. Cefazolin is a water-soluble (hydrophilic) antibiotic that does not penetrate adipose tissue regardless of IV dose. Importantly, adipose tissue is not a valid target tissue in clean-clean-contaminated SSI prophylaxis, as it does not become infected. Higher doses result in proportionately higher serum/non-adipose tissue concentrations, but adipose tissue concentrations are unaffected. Cefazolin displays time-dependent killing kinetics so that as long as serum/tissue concentrations are above the minimum inhibitory concentration (MIC) of SSI pathogens, there is no enhanced killing with higher concentrations relative to concentration-dependent antibiotics. Taking into account PK principles, a cefazolin 1 g IV bolus results in peak serum concentrations of ∼185 mcg/mL, provides at least six hours of intra-operative protection, aside from any post-antibiotic effects, and eliminates any rationale for intra-operative re-dosing for procedures lasting six hours or less. Some have argued that a cefazolin 3 g IV dose in the obese does not matter, as more must necessarily be better. However, from an antibiotic stewardship program (ASP) perspective, unneeded antibiotics are unnecessary. Moreover, the costs of cefazolin 1 g (IV push) at $0.75 versus 2 g (IV piggyback) at $ 6.83 can be significant in large centers using cefazolin prophylaxis for cardiothoracic, orthopedic, obstetric/gynecology, and bariatric surgery. Excessive antibiotics also expose the patient to potential adverse effects; i.e., Clostridium difficile. There is no dose-dependent or duration of exposure effect on resistance with one or two pre-operative or intra-operative doses. Well-done PK-based studies in obese patients clearly demonstrate the lack of benefit of using a 3-g dose or intra-operative re-dosing and show no incremental increase in adipose tissue concentrations with high doses. From an ASP point of view, antibiotic dosing recommendations should be reviewed and revised on the basis of PK principles that indicate that weight-based dosing has no basis for pre-operative prophylaxis in obese patients.

Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection.

BACKGROUND: The emergence of viral resistance is one of the greatest challenges in the treatment of HIV infection. Maraviroc is the first member of a new class of antiretroviral medications, the CCR5-receptor antagonists. It is approved by the US Food and Drug Administration (FDA) for use in combination with other antiretroviral agents in treatment-experienced patients infected with multidrug-resistant, CCR5-tropic HIV-1. OBJECTIVE: This article provides an overview of the pharmacology, efficacy, and tolerability of maraviroc in the treatment of HIV-1 infection. METHODS: Relevant information was identified through a search of MEDLINE (January 2000-May 2008) using the terms maraviroc, UK-427,857, and CCR5-receptor antagonist. Also consulted were abstracts from the International AIDS Society Conference, the Conference on Retroviruses and Opportunistic Infections, and other relevant scientific meetings. Additional publications were found by searching the reference lists of the identified articles and the FDA Web site. RESULTS: Maraviroc is a selective, reversible, small-molecule CCR5-receptor antagonist. In vitro, it has potent anti-HIV-1 activity, with a mean 90% inhibitory concentration of 2.0 nmol/L. It is widely distributed, with a V(d) of approximately 194 L. Maraviroc is moderately metabolized in the liver (65.3%), primarily via the cytochrome P450 3A4 isozyme. It has an elimination t(1/2) of 15.9 to 22.9 hours. Until more data are available, maraviroc should be avoided in patients with severe hepatic insufficiency; dose adjustment does not appear to be necessary on the basis of age, sex, or renal function. In 2 Phase IIb/III studies, maraviroc 300 mg PO QD or BID was found to be more efficacious than placebo in reducing the viral load at 48 weeks in treatment-experienced, CCR5-tropic HIV-1-infected patients receiving an optimized background regimen (difference vs placebo-QD arm: -0.89 log(10) copies/mL [97.5% CI, -1.17 to -0.62]; BID arm: -1.05 log(10) copies/mL [97.5% CI, -1.33 to -0.78]). The proportion of patients with a viral load < 50 copies/mL was 43.2% in the QD arm and 45.5% in the BID arm, compared with 16.7% in the placebo arm (P < 0.001, both treatment arms vs placebo). In treatment-naive patients infected with CCR5-tropic virus only, maraviroc 300 mg PO BID was not noninferior to oral efavirenz 600 mg QD (difference = -4.2%; lower bound of the 1-sided 97.5% CI, -10.9 [predefined statistical cutoff for noninferiority, -10]). Maraviroc was generally well tolerated in clinical trials. The most frequently reported (> or = 5%) adverse events were upper respiratory tract infection (20.0%), cough (12.7%), pyrexia (12.0%), rash (9.6%), musculoskeletal complaints (8.7%), gastrointestinal and abdominal pain (8.2%), dizziness (8.2%), appetite disorders (7.3%), insomnia (7.0%), herpes infection (6.8%), sinusitis (6.3%), joint complaints (6.1%), bronchitis (5.9%), and constipation (5.4%). The recommended dose of maraviroc differs based on concomitant medications, ranging from 150 to 600 mg BID. CONCLUSION: When used in combination with other antiretroviral agents, maraviroc appears to be a promising agent for treatment-experienced patients infected with multidrug-resistant, CCR5-tropic HIV-1.

Enhanced Efficacy of High Dose Oral Vancomycin Therapy in Clostridium difficile Diarrhea for Hospitalized Adults Not Responsive to Conventional Oral Vancomycin Therapy: Antibiotic Stewardship Implications.

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of "high dose" vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125-250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125-250 mg (PO) q6h), a "high dose escalation" dose group (250 mg → 500 mg (PO) q6h), and a "high dose" group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after "high dose" vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that "high dose" escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD.

Physical Screening Predictors for Success in Completing Air Force Phase II Air Liaison Officer Aptitude Assessment.

OBJECTIVES: Air Liaison Officer Aptitude Assessment (AAA) attrition is often associated with a lack of candidate physical preparation. The Functional Movement Screen, Tactical Fitness Assessment, and fitness metrics were collected (n = 29 candidates) to determine what physical factors could predict a candidate s success in completing AAA. METHODS: Between-group comparisons were made between candidates completing AAA versus those who did not (p < 0.05). Upper 50% thresholds were established for all variables with R2 < 0.8 and the data were converted to a binary form (0 = did not attain threshold, 1 = attained threshold). Odds-ratios, pre/post-test probabilities and positive likelihood ratios were computed and logistic regression applied to explain model variance. RESULTS: The following variables provided the most predictive value for AAA completion: Pull-ups (p = 0.01), Sit-ups (p = 0.002), Relative Powerball Toss (p = 0.017), and Pull-ups × Sit-ups interaction (p = 0.016). CONCLUSION: Minimum recommended guidelines for AAA screening are Pull-ups (10 maximum), Sit-ups (76/2 minutes), and a Relative Powerball Toss of 0.6980 ft × lb/BW. Associated benefits could be higher graduation rates, and a cost-savings associated from temporary duty and possible injury care for nonselected candidates. Recommended guidelines should be validated in future class cycles.

Daptomycin-induced hyperkalemia in a patient with normal renal function.

PURPOSE: A case of episodic hyperkalemia associated with daptomycin administration is reported. SUMMARY: A 46-year-old African-American woman was hospitalized for treatment of a shoulder abscess. Initially treated with i.v. vancomycin, the patient was switched to daptomycin 9 mg/kg i.v. (500 mg daily) after three days. On day 10 of daptomycin therapy, she was noted to have a serum potassium concentration of 5.4 meq/L, with an increase to 6.1 meq/L on day 11. Reversal of hyperkalemia was achieved with oral sodium polystyrene sulfonate and other agents, and daptomycin was withheld for one day, during which time the patient's serum potassium level normalized. One day after daptomycin therapy was resumed at a lower dose (7 mg/kg), the potassium concentration increased again (to 5.5 meq/L). With a further dosage reduction and continued administration of sodium polystyrene sulfonate, the patient completed the full course of daptomycin therapy. There was a close temporal relationship between daptomycin administrations and the serum potassium fluctuations; other potential causes of hyperkalemia were ruled out. Evaluation of this case using the algorithm of Naranjo et al. yielded a score of 6, indicating that the serum potassium elevations probably constituted an adverse reaction to daptomycin. A literature search identified no other reports of hyperkalemia associated with daptomycin use in a patient with normal renal function. CONCLUSION: A 46-year-old women with normal renal function developed hyperkalemia after receiving high-dose daptomycin therapy. The potassium levels normalized when daptomycin was withheld but increased again when the patient was rechallenged with the drug.