Search

The compositions of mantle-derived magmas indicate a substantial variety in the abundances of volatiles in the upper mantle. CO 2 and H 2 O depress the melting point of mantle peridotites considerably, delineating a pressure-temperature region of incipient melting where small degrees of melt exist over a large temperature range (~300 °C) before major melting begins. However, the chemical characterization of these melts in high-pressure experiments is challenging at low melt fractions (melt pockets may occupy volumes of only 10–50 μm3) because of analytical uncertainties related to the ubiquitous formation of metastable phases during quenching. This systematic partial melting study presents carefully determined compositions of incipient melts of a range of peridotites in the presence of CO 2 + H 2 O mixtures at 2.5 to 7 GPa. Four different fertile and depleted peridotites were used: Hawaiian pyrolite, K 2 O-enriched pyrolite, MORB pyrolite and depleted lherzolite. To arrive at accurate melt compositions, we introduce the melt tomography method that integrates multiple area scans of melt pockets polished to several depths. Results confirm that incipient and low degree melts progress abruptly (within 25 °C) from carbonatitic towards melilititic-nephelinitic compositions at 2.5 GPa, whereas they progress gradually from carbonate-rich to carbonated silicate (aillikitic) compositions at 4–5 GPa. Melt compositions at near-solidus conditions are mainly controlled by the breakdown of carbonate, and hydrous phases such as pargasite and phlogopite, and become less siliceous and slightly more magnesian with increasing pressure at given melt fractions. Melts exhibit strong increases in SiO 2 (2.75 to 44 wt%) with increasing temperature, whereas TiO 2 , Na 2 O and K 2 O decrease. The generally strongly potassic (K 2 O ≤ 6.63 wt%) and sodic (Na 2 O ≤ 3.06 wt%) character of the volatile-rich, incipient and low-degree melts indicate that these would act as reactive metasomatic agents that may transport large amounts of energy and induce chemical changes in large volumes of the upper mantle. • Melting experiments of 4 peridotitic starting compositions in presence of H2O + CO2. • Standardized melt tomography was developed to determine melt compositions. • Melts of enriched peridotites are carbonatite, aillikite and ultramafic lamprophyre. • Melts of depleted peridotite are melilitite, nephelinite and ultramafic lamprophyre. [ABSTRACT FROM AUTHOR]

Since the discovery of penicillin 80 years ago, gram-negative bacteria have become proficient at evading the lethal activity of β-lactam antibiotics, principally through the production of β-lactamases. The rapid emergence of penicillinases in both gram-positive and gram-negative bacteria led to the development of cephalosporin β-lactam antibiotics, but production of plasmid-mediated extended-spectrum cephalosporinases (or extended-spectrum β-lactamases) and AmpC enzymes resulted in resistance to this drug class. Because carbapenems were the only β-lactam agents active against such extended-spectrum β-lactamase-producing strains, appropriate and inappropriate use soon resulted in Enterobacteriaceae resistance. As a result, two distinct types of carbapenemases-the metallo-β-lactamases and Klebsiella pneumoniae carbapenemases (KPCs)-were soon identified. The KPCs comprise 10 variants that differ from one another by one to three amino acid substitutions (KPC-2 to KPC-11). The KPC-producing Enterobacteriaceae are not only multidrug resistant but are also difficult to detect routinely in the clinical microbiology laboratory. Tigecycline, polymyxins (colistin and polymyxin B), and aminoglycosides are possible candidate therapies for infections caused by KPC-producing organisms, although well-conducted clinical trials are required to fully define their roles in patient management. The shortage of new antimicrobial agents on the immediate horizon suggests that enhanced adherence with infection prevention procedures and antimicrobial stewardship programs are needed to curb patient-to-patient transmission and to reduce the selection of multidrug-resistant bacteria., (© 2012 Pharmacotherapy Publications, Inc.)

Background: The purpose of this study was to assess the incidence of candidemia in recipients of parenteral nutrition (PN) in a tertiary medical center with disease-specific guidelines for appropriate PN use., Methods: A retrospective, medical record/database review was conducted for adult patients who received PN in a 473-bed medical center from January 2006 to October 2008. Patients receiving PN >72 hours with no recent history of fungemia or concomitant antifungal therapy were evaluated for candidemia incidence with special interest in intensive care unit (ICU) patients. Epidemiological and clinical factors promoting candidemia development, pattern of systemic antifungal therapy use, and patient outcomes were investigated., Results: Of 286 PN recipients, 14 (4.9%) patients were diagnosed with new-onset candidemia, with an incidence rate of 1.6 episodes per 1000 hospital-days. In the subgroup of 177 ICU patients, 11 (6.2%) patients developed candidemia, with an incidence rate of 2.4 episodes per 1000 ICU-days. PN duration was significantly longer in the candidemia group, with a median of 17 (4-53) days compared with 8 (4-124) days in the noncandidemia group (P = .013). Severity of illness was defined as major to extreme in 83.5% of patients. Hospital mortality in the candidemia group was greater than in the noncandidemia group (35.7% vs 16.2%, P = .058)., Conclusions: Guidelines for PN therapy appropriately limit unnecessary use of PN but also select out severely ill patients who are at high risk for the development of candidemia. This study generates questions for future studies, including the benefits of empirical antifungal therapy in high-risk PN recipients.

Purpose: To address how the high endemic levels of antimicrobial resistance and multidrug resistance in hospitals have challenged clinicians to select appropriate therapy for effectively treating bacterial infections among seriously ill patients., Summary: Among gram-positive bacterial infections, differentiating between healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus infections is becoming more difficult and can seriously impact therapeutic strategies and hence outcomes. Furthermore, the rising prevalence of multidrug-resistant gram-negative bacterial infections is increasing the pressure on proper antimicrobial selection given the dearth of new antimicrobial agents under development. Optimized dosing strategies will be instrumental in minimizing emergence of resistance and preserving the utility of currently available agents. Antimicrobial stewardship programs in conjunction with stringent infection control policies will be critical in improving the appropriate use of antimicrobials while reducing the spread of nosocomial pathogens., Conclusion: Addressing the challenges of antimicrobial resistance in hospitals will require a multidisciplinary approach, with clinical pharmacists taking a proactive role in ensuring the appropriate use of antimicrobials.

Background: Limited data exist concerning characteristics of community-acquired Staphylococcus aureus infections (CA-SAI) in central and eastern Kentucky., Objective: To describe the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from January 1, 2004 through December 31, 2005, compare the number of CA-MRSA infections between years, and contrast treatment interventions and antibiotic susceptibility patterns of CA-SAI., Methods: A concurrent and retrospective study was conducted in 125 patients less than 18 years of age with CA-SAI admitted to the hospital/clinic based on criteria from the Centers for Disease Control and Prevention. Data on demographics, length of stay, antibiotic therapy, and antibiotic susceptibilities were collected., Results: Seventy patients were included for analysis (CA-MRSA, n = 51; community-acquired methicillin-susceptible S. aureus [CA-MSSA], n = 19). No statistically significant differences were noted between the number of CA-MRSA infections and the total CA-SAI (9/15 in 2004 vs 42/55 in 2005; p = 0.15). Approximately 75% of patients with CA-SAI were admitted to the hospital with no significant difference in length of stay. Ninety percent of CA-SAI were skin and soft tissue infections. There was a significant difference between groups with cutaneous abscesses (CA-MRSA, n = 37 vs CA-MSSA, n = 6; p = 0.002). Greater than 95% of all isolates were susceptible to vancomycin and trimethoprim/sulfamethoxazole. Half of CA-MRSA patients received inappropriate antibiotic therapy with beta-lactam antibiotics or clindamycin without confirmatory disk diffusion test. Twenty-five (49%) patients with CA-MRSA received surgical debridement (S/D) and/or incision and drainage (I/D) with concomitant antibiotic therapy. Four patients with CA-MRSA were rehospitalized for subsequent infections; all 4 received appropriate antibiotic therapy., Conclusions: A noticeable increase in CA-MRSA infections with cutaneous abscess between 2004 and 2005 was noted. In patients receiving inappropriate antibiotic therapy, treatment success was attributed to concomitant S/D and I/D. Further analysis should focus on the impact of antibiotic therapy alone or in combination with S/D and I/D on the incidence of subsequent CA-MRSA infections.

Objective: To assess the effect of prior antibiotic therapy on the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children., Methods: This was a concurrent and retrospective review of antibiotic records for children < 18 years of age with documented CA-MRSA infection identified between January 1, 2004, and December 31, 2005. Antibiotic records were compared against a control group. The primary outcome was the incidence of CA-MRSA using linear regression as a function of age and prior antibiotic therapy (i.e., 3 months prior to admission). Secondary objectives included a comparison of antibiotic courses and classes and a description of antibiotic susceptibilities in patients with CA-MRSA RESULTS: Data from 26 patients were included. Nine out of 51 patients (18%) with CA-MRSA were included. Another 17 children were enrolled in the control group. The median age was approximately 1.75 years (0.08-14 years) in the CA-MRSA group versus 2.75 years (0.005-15 years) in the control group. A statistical difference was noted in the number of patients with prior antibiotic exposure between the CA-MRSA and control group, 8 (88.9%) versus 6 (35.3%), respectively (P = .01). Antibiotic exposure was found to be a significant independent risk factor (P = .005; 95% CI, 0.167-0.846) for the development of CA-MRSA. The interaction between antibiotic exposure and age < 3 was the most significant predictor of CA-MRSA (P = .019; 95% CI, 0.139-1.40)., Conclusions: Prior antibiotic therapy in patients < 3 years of age was associated with a significant risk of developing CA-MRSA. A comprehensive assessment of CA-MRSA patients should include objective methods of measuring prior antibiotic exposure such as pharmacy records.

As more and more gram-negative bacteria produce extended-spectrum beta-lactamases, it is important that physicians know what to do when these bacteria cause postoperative infections in patients.

Objective: To review the efficacy of macrolides and tetracyclines in several chronic inflammatory conditions., Data Sources: Searches of MEDLINE (1966-March 2004) and an extensive bibliography search were undertaken. Key terms included acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis., Study Selection and Data Extraction: Data were obtained primarily from randomized placebo-controlled trials upon which key recommendations are based., Data Synthesis: Antibiotics are often prescribed for months or even years for treatment of chronic inflammatory conditions such as acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis. Randomized controlled trials have shown that azithromycin is useful in the management of cystic fibrosis and the tetracyclines are beneficial in the management of rheumatoid arthritis, acne, blepharitis, and periodontitis. Several large, randomized controlled trials have failed to show any benefit of macrolides in the secondary prevention of cardiovascular disease. No randomized placebo-controlled clinical trials have been performed to assess the efficacy of macrolides or tetracyclines in patients with rosacea., Conclusions: The use of tetracyclines and macrolides for rosacea is based primarily on anecdotal reports or open-label trials. Limited clinical trials support the use of tetracyclines or macrolides in acne, blepharitis, periodontitis, rheumatoid arthritis, and cystic fibrosis. Trials to date do not support the use of antibiotics for secondary prevention of cardiovascular disease.

Postoperative infections in joint prostheses and fracture-fixation devices commonly involve both MRSA and methicillin resistant coagulase-negative staphylococcus. In addition, community-acquired MRSA has also become an important consideration when infected patients are admitted to the hospital from the community. Preoperative colonization with MRSA and methicillin resistant coagulase-negative staphylococcus increases the risk of postoperative surgical site infections in orthopedic patients. Up to 5.3% of orthopedic patients are colonized with these organisms on hospital admission. Screening and decolonization of methicillin resistant staphylococci decrease the incidence of postoperative surgical site infections in the orthopedic patient. This may be particularly important in orthopedic implants given the difficulty encountered in treating infected prosthesis. Current US guidelines advocate screening for methicillin resistant staphylococci only when risk factors are present. Growing evidence suggests that screening and decolinization of all patients having elective orthopedic procedures, especially those including prosthetic implants, will decrease the incidence of postoperative infections. The infected prosthesis may be potentially salvaged if the clinical manifestations of infection have been present for < or = 10 days, the implant is stable, and the etiologic organisms are susceptible to oral antibiotics.

The University of Kentucky Hospital investigated the feasibility of choosing a sole fluoroquinolone for its formulary in an effort to reduce costs without affecting clinical outcomes. A three-step process was used to plan, implement, and monitor the selection program. Based on the range of clinical indications, safety profile, local susceptibility, cost, and dosing convenience, levofloxacin was chosen over ciprofloxacin and gatifloxacin as the sole fluoroquinolone. Since the implementation of the program in May 2001, susceptibility to levofloxacin has been maintained or increased for the most common pathogens. In addition, University Hospital has saved nearly 100,000 dollars in antibiotic acquisition costs during the first 12 months after the switch. This assessment did not take into account effects in clinical outcomes, such as clinical failures (such as readmission rates), mortality, and adverse events, or measure changes in overall medical expenditures beyond drug acquisition costs. In the future, monitoring of overall patient care and medical care costs, in addition to susceptibility patterns and drug costs, will allow for a better understanding of the long-term benefits of this switch.

The frequency of invasive fungal infections (IFIs) has increased with the increase in number of high-risk patients. United States trends in mortality due to invasive mycoses showed a striking increase in the past 2 decades. Human immunodeficiency virus-associated opportunistic mycoses accounted for part of the increase, as did mycoses in other immunocompromised populations. Those at-risk populations include recipients of solid organ transplants or hematopoietic stem cell transplants, those with hematologic malignancies, and others receiving immunosuppressive treatment. Infections due to Candida sp are the most common fungal infections. The mortality rate due to invasive aspergillosis has risen steadily, with a 357% increase from 1980-1997. Depending on whether an IFI is possible, probable, or proved, three treatment strategies are available: prophylactic, empiric, and specific. Options for preventing and treating IFIs have increased, with four classes of antifungal agents available: polyenes, azoles, nucleoside analogs, and echinocandins. The effectiveness of the polyene amphotericin B deoxycholate (the standard for > 40 yrs) is limited by toxic effects, notably renal and infusion-related toxicity. Three lipid formulations are approved for the treatment of IFIs in patients refractory to or intolerant of amphotericin B: amphotericin lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B. The nucleoside analog class contains only flucytosine--an antimetabolite targeting the nucleus of the fungal cell and generally not given as monotherapy because of frequent development of resistance. The azoles debuted with ketoconazole, followed by fluconazole, itraconazole, and voriconazole. Fluconazole is largely active against Candida sp and Cryptococcus neoformans; itraconazole's activity is largely against moulds, such as Aspergillus, and dimorphic fungi, such as Histoplasma and Blastomyces; and voriconazole is active against both yeasts and moulds. The echinocandin class has one drug approved for clinical use--caspofungin, which targets the fungal cell wall. Deciding which antifungal agent to use involves weighing such clinical factors as mycoses susceptibility and drug toxicity, as well as pharmacoeconomic considerations. Besides the price of the drug, the cost of antifungal therapy includes costs of mortality associated with failed treatment, prolonged hospitalization and treatment related to complications, and additional antifungal treatment to compensate for primary treatment failure.

The tectonic setting in which the first continental crust formed, and the extent to which modern processes of arc magmatism at convergent plate margins were operative on the early Earth, are matters of debate. Geochemical studies have shown that felsic rocks in both Archaean high-grade metamorphic ('grey gneiss') and low-grade granite-greenstone terranes are comprised dominantly of sodium-rich granitoids of the tonalite-trondhjemite-granodiorite (TTG) suite of rocks. Here we present direct experimental evidence showing that partial melting of hydrous basalt in the eclogite facies produces granitoid liquids with major- and trace-element compositions equivalent to Archaean TTG, including the low Nb/Ta and high Zr/Sm ratios of 'average' Archaean TTG, but from a source with initially subchondritic Nb/Ta. In modern environments, basalts with low Nb/Ta form by partial melting of subduction-modified depleted mantle, notably in intraoceanic arc settings in the forearc and back-arc regimes. These observations suggest that TTG magmatism may have taken place beneath granite-greenstone complexes developing along Archaean intraoceanic island arcs by imbricate thrust-stacking and tectonic accretion of a diversity of subduction-related terranes. Partial melting accompanying dehydration of these generally basaltic source materials at the base of thickened, 'arc-like' crust would produce compositionally appropriate TTG granitoids in equilibrium with eclogite residues.

Drug acquisition cost is an important component in the analysis of economic and clinical outcomes in the treatment of respiratory tract infections (RTIs). However, bacterial resistance has emerged as a crucial variable that must also be considered. Drug-resistant infections result in more expensive drug therapy, longer hospital stays, and increased mortality. The high prevalence of community-acquired pneumonia (CAP), as well as the continuing growth in resistant pathogens, make RTIs an appropriate model for studying methods of cost-containment without sacrificing clinical outcome. The University of Kentucky Medical Center has developed a uniform CAP treatment pathway to minimize costs and maximize outcomes. First-line therapy in this model is doxycycline monotherapy, high-dose amoxicillin plus azithromycin, or levofloxacin monotherapy. One major future concern in selecting antibacterial agents for CAP is the spread of macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae.