Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Impact of a pharmacy department-wide transitions-of-care program on inappropriate oral antibiotic prescribing at hospital discharge.

Objective: To evaluate oral antibiotic prescribing for common infections at hospital discharge before and after implementation of a pharmacist-driven transitions-of-care (TOC) program. Design: Single-center before-and-after study. Setting: Acute-care, academic, community hospital in Santa Barbara, California. Patients: Eligible adult patients prescribed oral antibiotics at hospital discharge for community-acquired pneumonia, skin and soft-tissue infections, and urinary tract infections between September 2019 and December 2019 (preimplementation period) and between March 2021 and May 2021 (postimplementation period). Intervention: Antimicrobial stewardship-initiated, department-wide, TOC program requiring all clinical pharmacists to review discharge antibiotic prescriptions in real time. Results: In total, 260 antibiotic prescriptions were assessed for appropriateness: 140 before implementation and 120 after implementation. After implementation, the number of prescriptions considered inappropriate significantly decreased by 18% (52% vs 34%; P = .005). Inappropriate rates decreased in all assessment categories: dosing (15% vs 2%; P < .001), treatment duration (42% vs 31%; P = .08), antibiotic selection based on infection type or microbiology (8% vs 4%; P = .33), and antibiotics not indicated (16% vs 10%; P = .18). Median total antibiotic days decreased by 1 day after implementation (10 days vs 9 days; P = .67), and 30-day readmission rates were similar between both phases. Conclusions: A real-time, pharmacist-driven, TOC program for oral antibiotic prescriptions had a significant impact in reducing inappropriate prescribing of antibiotics at hospital discharge for common infections. Incorporating discharge antibiotic prescription review into pharmacist daily workflow may be a sustainable approach to outpatient antimicrobial stewardship in a setting with limited resources.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Assessing Preceptor and Student Perceptions of Remote Advanced Pharmacy Practice Experience Learning during the COVID-19 Pandemic.

The coronavirus disease 2019 pandemic created a major shift in learning modalities in the Advanced Pharmacy Practice Experience program. This descriptive study aimed to evaluate preceptor and student perceptions of remote learning experiences and student practice readiness upon completion of remote rotations. Preceptors and students who participated in partial to full remote experiential rotations between 17 August 2020 and 26 March 2021 were invited to complete an on-line survey. A cross-sectional survey consisted of closed-ended questions using a 5-point Likert scale assessing perception on adaptability, effectiveness of remote learning in advancing practice knowledge and skills, and confidence in students' practice readiness. A total of 29 preceptors and 43 students completed the survey (response rates of 67% and 57%, respectively). Approximately 70% of the remote rotations were practice-based, with ambulatory care representing the most frequently reported rotation by preceptors (38%) and students (28%). A high level of confidence in preceptor perception of their ability to adapt and provide effective remote experiences (average 4.28) matched with the students' high level of confidence with their preceptors' abilities (86% agree or strongly agree). Upon the completion of remote rotations, both preceptors and students felt confident in student practice readiness based on student ability to design and initiate individualized patient care plans or complete projects using evidence-based resources (79% and 86%, respectively). Most preceptors (69%) reported that students achieved the rotation objectives at the same level as students engaged in-person experiences. The limitations of remote learning included the absence of direct interactions. Overall, both preceptors and students reported achieving practice readiness with remote experiential learning experiences and felt the remote activities should be continued post-pandemic.

Challenges in Treating Chlamydia trachomatis, Including Rectal Infections: Is It Time to Go Back to Doxycycline?

OBJECTIVE: To evaluate recent publications on efficacy of single-dose azithromycin and 7-day doxycycline when treating Chlamydia trachomatis. DATA SOURCES: A literature search of MEDLINE, EMBASE, PubMed, and Cochrane library was conducted (1990 to June 13, 2021) using the terms: Chlamydia trachomatis, genital chlamydia, rectal chlamydia, extragenital chlamydia, azithromycin, doxycycline, and treatment guidelines. ClinicalTrials.gov was searched to identify ongoing trials. STUDY SELECTION AND DATA EXTRACTION: English language studies, including controlled studies, retrospective analyses, systematic reviews, meta-analyses, and case reports, reporting microbiological or clinical outcomes in adolescents and adults were considered. DATA SYNTHESIS: Systemic reviews and meta-analyses of randomized trials reported azithromycin efficacy of 96% to 97% in genital chlamydia. However, reports of treatment failure have emerged, especially among symptomatic males, with an increased risk of microbiological failure after azithromycin than doxycycline (relative risk = 2.45; 95% CI = 1.36-4.41). Retrospective analyses and prospective observational cohort studies reported lower efficacy range following azithromycin than doxycycline (74%-87% vs 92%-100%, respectively) in rectal chlamydia. First randomized controlled trial comparing azithromycin and doxycycline reported significantly higher microbiological cure following doxycycline, with absolute difference of 26% (95% CI = 16%-36%; P < 0.001). The proposed 2021 Centers for Disease Control and Prevention treatment guidelines designate doxycycline as the preferred agent for treatment at any site. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: A growing body of evidence for treatment failure following azithromycin, especially in rectal chlamydia supports updating current practice. CONCLUSIONS: Doxycycline continues to achieve high efficacy in genital and rectal chlamydia. Clinicians should consider efficacy with convenience of dosing regimen, medication compliance, and sexual behavior risks when treating chlamydia infections.

Adapting pharmacy experiential education during COVID-19: Innovating remote preceptor resources, tools, and patient care delivery beyond virtual meetings.

PURPOSE: To describe the innovative teaching practices, tools, and resources for remote learning developed by a school of pharmacy with a decentralized experiential program to empower and support preceptors in response to the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY: As the pandemic has continued, there have been significant shifts in pharmacy workflow, staffing, and patient care delivery. Pharmacy students are slowly being reintegrated into these learning environments. Although preceptors are willing and eager to teach, many lack the resources, tools, and support to create remote learning experiences at their facilities. The University of the Pacific Thomas J. Long School of Pharmacy has a decentralized experiential education model in which faculty regional coordinators with clinical practices and diverse expertise are disseminated throughout California. This model allowed us to collaborate and understand preceptor needs from a local level. We created a preceptor COVID-19 guidance document, introduced innovative virtual playbooks to pivot up to 100% remote rotations, and promoted the layered learning model to integrate pharmacy residents into the remote teaching space. Communication and flexibility are key to ensure student and preceptor safety while maintaining high-quality advanced pharmacy practice experiences and preserving patient-student relationships in telehealth. CONCLUSION: Overall, we successfully created innovative solutions and leveraged our decentralized experiential model to meet the teaching and learning demands during an unanticipated crisis. We continue to adapt and plan to assess the effectiveness of the tools by administering surveys of preceptors and pharmacy students.

Role of rapid diagnostics for viral respiratory infections in antibiotic prescribing decision in the emergency department.

OBJECTIVE: To describe the frequency of antibiotic prescriptions in patients with known viral respiratory infections (VRIs) diagnosed by polymerase chain reaction (PCR) in 3 emergency departments (EDs) and to identify patient characteristics that influence the prescribing of antibiotics by ED physicians despite PCR confirmation of viral cause. DESIGN: Retrospective, observational analysis of patients with PCR-diagnosed VRI discharged from 3 acute-care hospital EDs within 1 health system. RESULTS: In total, 323 patients were discharged from the ED with a VRI diagnosis, of whom 68 were prescribed antibiotics (21.1%). These patients were older (median, 59.5 vs 43 years; P = .04), experienced symptoms longer (median, 4 vs 2 days; P = .002), were more likely to have received antibiotics in the preceding 7 days (27.9% vs 9.8%; P < .001), and had higher proportions of abnormal chest X-rays (64.5% vs 28.4%; P < .001). Patients were more likely to receive antibiotics for a diagnosis of pneumonia (39.7% vs 1.6%; P < .001) or otitis media (7.4% vs 0.4%; P = .002), and were less likely with diagnosis of upper respiratory infection (2.9% vs 13.7%; P = .02) or influenza (20.6% vs 44.3%; P < .001). CONCLUSIONS: Despite a diagnosis of VRI, one-fifth of ED patients were prescribed antibiotics. Patient characteristics including age, duration of symptoms, abnormal chest X-rays, and specific diagnosis may increase provider concern for concurrent bacterial infections. Opportunities exist for antimicrobial stewardship strategies to incorporate rapid diagnostics in promoting judicious antibiotic usage in the ED.

HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.

Living with advanced cancer and the role of the primary care provider: The missing piece in the survivorship discourse.

The period of survivorship has been identified as a distinct phase of the cancer continuum, and the key role of primary care providers in caring for cancer survivors has been recognized. However, much of the focus to date has been placed on cancer survivors who are treated with curative intent and survive cancer-free. Receiving less attention are those who are living with advanced, non-curative cancer. In this commentary, we review the current evidence about the characteristics of these survivors, their unmet needs and receipt of health care. We offer insights into future research, education and policy initiatives aiming to enhance the care for this population.

Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus.

The frequency of syphilis has been increasing during the past 5 years primarily among men who have sex with men, many of whom are infected with the human immunodeficiency virus (HIV). Data on treatment options other than intravenous or intramuscular penicillin for syphilis are very limited. We describe two HIV-infected patients with asymptomatic neurosyphilis who were successfully treated with oral doxycycline. The first patient was a 45-year-old Hispanic man with well-suppressed HIV RNA who had a positive Venereal Disease Research Laboratory (VDRL) titer of 1:128. His cerebral spinal fluid (CSF) revealed a positive VDRL titer of 1:16, and an elevated white blood cell count of 96 cells/mm(3) and protein level of 89 mg/dl. He received high-dose doxycycline 200 mg twice/day for 28 days. Two months later, his CSF VDRL titer, white blood cell count, and protein level decreased to 1:4, 5 cells/mm(3), and 60 mg/dl, respectively. The second patient was a 37-year-old Caucasian man with complications from acquired immunodeficiency disease. A routine VDRL titer was found to be 1:64. Although the CSF VDRL was nonreactive, both his white blood cell count and protein level were elevated at 29 cells/mm(3) and 46 mg/dl, respectively. High-dose doxycycline 200 mg twice/day was prescribed for 28 days. Three months later, the patient's VDRL titer decreased to 1:2; his CSF white blood cell count decreased significantly to 1 cell/mm(3), and his protein level was within normal limits. Clinicians should be aware that an extended course of high-dose, oral doxycycline may be an effective and safe alternative regimen to intravenous or intramuscular penicillin, without requiring hospitalization or home health care, for the treatment of neurosyphilis in HIV-infected patients. Prospective trials are needed to assess the long-term efficacy oral doxycycline for neurosyphilis.

Mycobacterium szulgai in a patient with advanced acquired immunodeficiency syndrome: an unusual pathogen with unusual multidrug resistance.

A 37-year-old Hispanic man with advanced acquired immunodeficiency syndrome developed extensive pulmonary disease with persistent cough, fever, night sweats, worsening dyspnea, and weight loss. Sputum samples showed scant growth of acid-fast bacilli. He failed to respond to the standard tuberculosis regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. Subsequently, Mycobacterium szulgai was identified, and susceptibility tests showed it to be resistant to all four of those agents. Therapy was changed to clarithromycin, doxycycline, ciprofloxacin, and amikacin. Within 2 weeks, the patient's condition improved significantly, and 6 months after treatment, extensive pulmonary infiltrates had nearly resolved. Fewer than 1% of all human isolates of mycobacteria consist of M. szulgai, which is relatively susceptible to standard antimycobacterial agents. To our knowledge, this is the first reported case of M. szulgai with resistance to all primary antituberculosis drugs.

Analysis of human choriogonadotropin core 2 o-glycan isoforms.

Measurements of human choriogonadotropin (hCG) isoforms containing core 2 o-glycans may be useful for diagnosis of Down Syndrome pregnancies and trophoblastic disease. As shown here, this isoform is also present in pituitary extracts, early pregnancy urine, and urine of postmenopausal women. Although, measurements of hCG isoforms may be useful in several clinical settings, this remains to be determined due to the lack of suitable standards and the difficulties of comparing data obtained in different laboratories. Here, we report that monoclonal antibodies B152 and CTP104 recognize the third (Ser132) and fourth (Ser138) o-glycans, respectively, in the carboxyterminal portion of the hCG beta-subunit. The proximity of these sites prevents B152 and CTP104 from binding simultaneously to isoforms containing core 2 o-glycans. Unlike B152, which binds only the core 2 isoform, CTP104 recognizes both glycan moieties. By measuring hCG with CTP104 in the presence and absence of B152, one can quantify both isoforms using the same readily available standard.

The ISOBM TD-7 Workshop on hCG and related molecules. Towards user-oriented standardization of pregnancy and tumor diagnosis: assignment of epitopes to the three-dimensional structure of diagnostically and commercially relevant monoclonal antibodies directed against human chorionic gonadotropin and derivatives.

The ISOBM TD-7 hCG Workshop was established to characterize the molecular epitope structure and specificities of a panel of diagnostically relevant monoclonal antibodies (MAbs) directed against human chorionic gonadotropin (hCG) and its derivatives, and to consider how this information could be used to improve comparability of immunoassay results for these analytes. In this multicenter study, 27 MAbs have been characterized in detail as to their main and fine specificities by direct binding-, competitive- and sandwich-RIA, -ELISA, BIAcore and Western blotting. Antigens used in the study included the upcoming first WHO reference reagents for immunoassay, i.e. nick-free hCG (hCG), nicked hCG (hCGn), hCG alpha-subunit (hCGalpha), hCG beta-subunit (hCGbeta), nicked hCG beta-subunit (hCGbetan), hCG beta-core fragment (hCGbetacf), synthetic peptides of hCGbeta C-terminal peptide (hCGbetaCTP), and homologous hormones, luteinizing hormone (LH) and subunits (LHbeta) from various species. Correct classification of blinded internal controls demonstrated the reliability of the MAb referencing approach. Three-dimensional molecular epitope assignment was possible in many instances by comparing immunoreactivity of the ISOBM MAbs (n = 27) to a large panel of MAbs (n = 18) previously well characterized in the Innsbruck (P.B.) and Paris (J.M.B.) laboratories. All three major antibody specificities (alpha, n = 1; beta, n = 21; alphabeta, n = 5) were represented in the TD-7 MAb panel. HCGbeta MAbs could further be subdivided into (i) those recognizing hCGbeta only (epitopes: beta(6), n = 1; beta(7), n = 2; beta(14), n = 1) and (ii) those recognizing hCGbeta + hCG (beta1, beta2, beta4, beta5, n = 10; beta8 and beta9, n = 9). Members of the latter group were specific either for hCG + hCGbeta + hCGbetacf (beta1, n = 3) or hCG + hCGbeta + hCGbetaCTP (beta8, n = 6; beta9, n = 1) or in addition to hCG + hCGbeta + hCGbetacf recognized hLH/hLHbeta to a minor (beta2, n = 3; beta4, n = 3) or similar degree (beta5, n = 1). Epitopes were (i) located on the first and third loops protruding from the cystine knot of hCGbeta (beta2-beta6, aa hCGbeta20-25 and 68-77), (ii) presumably centered around the knot itself (beta1), or (iii) on hCGbetaCTP (epitope beta8 = hCGbeta141-144, beta9 = hCGbeta113-116). The ISOBM panel of MAbs represents all major epitope specificities suitable for the design of specific sandwich immunoassays. High analyte variability in serum and urine during the course of pregnancy and tumor development favors certain epitope combinations. For routine diagnostic purposes, assays recognizing a broad spectrum of hCG/hCGbeta variants such as hCG + hCGn + hCGbeta + hCGbetan + hCGbetacf + -CTPhCG + -CTPhCGbeta may be useful. Low cross-reactivity against related glycoprotein hormones (e.g. hLH) and their derivatives is mandatory. These criteria are best met by combinations of MAbs directed against epitopes located around the cystine knot (beta1) and against those encompassing the top of loops 1 and 3 on hCGbeta (beta2, beta4). The first WHO reference reagents for immunoassay of hCG and hCG-related molecules being prepared by the IFCC should facilitate characterization of what assays for 'hCG' are measuring. The next step towards improving between-laboratory comparability of measurements of hCG/hCG derivatives in pregnancy and oncology is provided by results of this TD-7 Workshop.

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope.

Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

Immunochemical measurement of early pregnancy isoforms of HCG: potential applications to fertility research, prenatal diagnosis, and cancer.

Human chorionic gonadotropin, the glycoprotein hormone of pregnancy, is found naturally in blood and urine in a variety of isoforms. These variants are related to both peptide bond cleavages (such as the nicked forms of hCG) and the beta core fragment urinary metabolite, as well as the larger variety of species resulting from carbohydrate heterogeneity. We have recently developed immunoassay systems that can measure nicked forms of hCG (antibody B151) as well as particular high carbohydrate variants (hyperglycosylated forms) of hCG (B152), which are associated with cancers producing hCG. Using the assay system for nicked hCG, we found that nicked hCG does not appear to be present as a significant hCG isoform during normal pregnancies if the urine specimens are well preserved. Applying the assay for hyperglycosylated hCG isoforms, we discovered that these forms are prevalent during very early pregnancy and decline rapidly to low concentration after the first 6 weeks of pregnancy. Persistence of these early pregnancy forms does not bode well for the pregnancy. Other investigators report that measurement of such hCG isoforms may aid in diagnosis of Down syndrome pregnancies. In summary, measurement of the hyperglycosylated hCG isoforms are useful for evaluation of healthy progress of normal pregnancy, as an additional detection marker for Down syndrome pregnancies, and as a potential new marker of trophoblastic malignancy. New reference preparations will soon be available for the calibration of assay systems for measurement of many of these hCG variants and metabolites.

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production.

The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH beta core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH beta core is the same as the pituitary-extracted hLH beta core, beta 6-40 disulfide bridged to beta 55-93, except that the pituitary core is more heterogeneous containing also beta 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG beta core with a primary structure identical to that of the human CG beta core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.

Comparative in vitro activity of vancomycin and levofloxacin in combination with rifampin against planktonic versus sessile cells of Staphylococcus epidermidis.

STUDY OBJECTIVE: To evaluate the activity of vancomycin and levofloxacin alone and combined with rifampin against planktonic and sessile cells. INTERVENTION: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the three drugs were determined against a clinical isolate of methicillin-resistant Staphylococcus epidermidis (MRSE 23) and a reference strain of MRSE (ATCC 35984). MEASUREMENTS AND MAIN RESULTS: The MICs/MBCs of vancomycin, levofloxacin, and rifampin against MRSE 23 were 0.78/0.78 microg/ml, 0.19/0.19 microg/ml or below, and 0.19/0.19 microg/ml or below, and against ATCC 35984 were 0.78/1.56 microg/ml, 0.19/0.19 microg/ml or below, and 0.19/0.19 microg/ml or below, respectively. A 99.9% killing activity was achieved with vancomycin, levofloxacin, and vancomycin-levofloxacin against planktonic cells of MRSE 23 (18.9, 21.3, and 17.5 hrs, respectively) and only with levofloxacin against ATCC 35984 (21.5 hrs). No regimen achieved 99.9% killing activity against sessile cells. CONCLUSION: Adding rifampin was antagonistic against planktonic cells and had an additive effect against sessile cells. Activity typically reported using nutrient-rich, planktonic cells may not be applicable to sessile cells under environmental and growth restrictions.

Preparation and analysis of the common urinary forms of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) is the hormone of pregnancy and forms the basis of all pregnancy tests as well as diagnostic assays for a variety of pathological states including certain types of cancers and some diseases of pregnancy and genetic abnormalities. In recent years, the discovery of the diagnostic utility of measurement of the free subunits and fragments of the hormone, especially in urine, has proven of special use for diagnosis of very early pregnancy loss, an important phenomenon related to infertility, as well as part of screening programs for Down Syndrome and gynecological cancers. This article summarizes existing and new methods for the preparation of hCG, its subunits, and the beta core fragment from urinary sources. The methods for proper analyses of these materials are also described to enable investigators to prepare and analyze these materials in various quantities in their own laboratories.

Differences in urinary excretion patterns of the hLH beta core fragment in premenopausal, perimenopausal, and postmenopausal women.

OBJECTIVE: The heterodimeric luteinizing hormone beta core fragment (hLH beta cf) is a highly stable urinary analyte reflective of circulating hLH. It is measured easily because of its high molar content and has none of the multiple isoforms and subunit dissociation problems of LH urinary measurements. As part of a long-term effort to develop new biochemical assays to stage women during the perimenopausal transition, we have examined the patterns of urinary excretion of this metabolite of hLH in premenopausal, perimenopausal, and postmenopausal women. DESIGN: We measured the concentration of the hLH beta cf in 10 consecutive first morning void urine specimens from premenopausal, perimenopausal, and postmenopausal women. Day 1 of collection was the first day of menses in the cycling women. RESULTS: Postmenopausal women exhibited a widely fluctuating pattern of LH beta core fragment excretion, which is not correlated with hLH measured by immunofluorometric assay or with follicle-stimulating hormone measured by immunofluorometric assay. The postmenopausal group was easily distinguished from premenopausal women on the basis of an area-under-the-curve concentration function. Perimenopausal women displayed intermediate hLH beta cf concentrations; some clearly were in postmenopausal ranges, and others were in the premenopausal ranges. CONCLUSIONS: The pattern of excretion and concentrations of the hLH beta cf is significantly different between premenopausal and postmenopausal women. Perimenopausal women exhibited intermediate changes. The capability to measure this type of stable urinary metabolite as a reflection of changes in dynamics of its parent circulating hormone offers new possibilities in the development and application of large-scale testing that does not require blood sampling.