Experience implementing a university-based mass immunization program in response to a meningococcal B outbreak.

Neisseria meningitidis serogroup B (MenB) has caused several recent outbreaks of meningococcal disease on US college campuses. In January 2015, a case of MenB was reported at a university in Oregon, culminating in an outbreak with a total of 7 cases (including 1 fatality) identified over a 5-month period. In response to the outbreak, the university organized a mass immunization campaign with 4 "opt-in" immunization clinics.

Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis.

Background: The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

Methods: We conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia.

Clinical population pharmacokinetics and toxicodynamics of linezolid.

Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity.

Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: a pooled data analysis.

Phase III randomized, clinical trials are primarily designed to evaluate overall treatment-outcome comparisons. Although valuable data are gained from such comparisons, it is difficult to draw meaningful inferences about potential outcomes differences in specific patient groups and infection types. It is well established that clinical outcomes are dependent on host, treatment- and pathogen-related factors and understanding which groups benefit from one treatment relative to another is of great importance.

The impact of linezolid versus vancomycin on surgical interventions for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus.

Background: We conducted a study with the primary objective of assessing whether a difference existed in the frequency and type of surgical interventions (SIs) implemented in patients treated with linezolid versus vancomycin for the management of complicated skin and skin structure infections (cSSSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA).

Methods: We analyzed data from a phase IV clinical trial evaluating the safety and efficacy of linezolid and vancomycin, given for 7-14 d, to treat cSSSIs other than cellulitis that were caused by MRSA. The study included patients who received ≥1 dose of drug, had a cSSSI caused by culture-proved MRSA, and underwent ≥1 SI after commencement of the study.

Population pharmacokinetic evaluation with external validation and Bayesian estimator of voriconazole in liver transplant recipients.

Objectives: The objectives of this study were to evaluate the pharmacokinetics of voriconazole in liver transplant patients, probe covariate effects on voriconazole pharmacokinetics, externally validate the model and explore limited sampling strategies (LSSs) using Bayesian approaches.

Methods: Full pharmacokinetic profiles were collected within one oral dosing interval from 13 liver transplant patients. Nonlinear mixed-effects pharmacokinetic models were developed using NONMEM software.

Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients.

Background: Inhaled amphotericin preparations have been used for prophylaxis against invasive aspergillosis in lung transplant recipients. However, no published data exist regarding the pharmacokinetic profile of amphotericin B lipid complex in lung transplant recipients.

Methods: We prospectively determined the concentrations of amphotericin B in the epithelial lining fluid (ELF) and plasma after aerosolized nebulization (AeroEclipse), of amphotericin B lipid complex at 1 mg/kg every 24 hr for 4 days in 35 lung transplant recipients.

Suboptimal aminoglycoside dosing in critically ill patients.

Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by > or =10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed.

Optimizing use of aminoglycosides in the critically ill.

In the era of increasing bacterial resistance and a lack of development of new antimicrobials for the treatment of gram-negative infections, aminoglycosides (AGs) are more commonly used in combination with other antimicrobials for the treatment of life-threatening infections in the intensive care unit (ICU). AGs display concentration-dependent killing activity; thus the rate and extent of bacterial killing increase with increasing peak (Cmax) drug concentrations. Optimizing AG dosing requires attainment of a pharmacodynamic target ratio (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is associated with a more rapid rate of resolution of infection.

Acquisition of rectal colonization by vancomycin-resistant Enterococcus among intensive care unit patients treated with piperacillin-tazobactam versus those receiving cefepime-containing antibiotic regimens.

In contrast to expanded-spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations such as piperacillin-tazobactam have rarely been associated with vancomycin-resistant Enterococcus (VRE) colonization and infection. In mice, piperacillin-tazobactam has sufficient antienterococcal activity to inhibit the establishment of colonization during treatment, but this effect has not been confirmed in human patients. We prospectively evaluated the acquisition of rectal colonization by VRE among intensive care unit patients receiving antibiotic regimens containing piperacillin-tazobactam versus those receiving cefepime, an expanded-spectrum cephalosporin with minimal antienterococcal activity.

Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms.

For commonly encountered gram-negative bacilli, a MIC of cefepime of 8 mug/ml or less was defined by the Clinical and Laboratory Standards Institute as "susceptible" prior to the commercial release of the antibiotic. We assessed 204 episodes of bacteremia caused by gram-negative organisms for which patients received cefepime (typically 1 to 2 g every 12 h) as the primary mode of therapy. The cefepime MIC breakpoint derived by classification and regression tree (CART) software analysis to delineate the risk of 28-day mortality was 8 microg/ml.

Pseudomonas aeruginosa infections in the Intensive Care Unit: can the adequacy of empirical beta-lactam antibiotic therapy be improved?

Inadequate empirical antibiotic therapy for serious Pseudomonas aeruginosa infections has been linked to increased mortality. We performed a retrospective cohort study of consecutive patients with ventilator-associated pneumonia, bacteraemia or other sterile-site infections caused by P. aeruginosa occurring during Intensive Care Unit admissions.

Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.

Objectives: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A.

Epidemiological profile of linezolid-resistant coagulase-negative staphylococci.

Background: Surveillance studies have shown that <0.1% of coagulase-negative staphylococci are linezolid resistant; however, at our institution, 4% of such organisms were found to be resistant. We investigated the risk factors for and the epidemiological profile of linezolid-resistant coagulase-negative staphylococci.

Intrapulmonary penetration of voriconazole in patients receiving an oral prophylactic regimen.

Voriconazole penetrated well into the pulmonary epithelial lining fluid (ELF) in lung transplant patients receiving oral prophylaxis. The ELF concentrations exceeded those of the plasma, with an average ELF-to-plasma ratio of 11 (+/-8). A strong association between plasma and ELF concentrations (r(2) = 0.

Meropenem administered as a prolonged infusion to treat serious gram-negative central nervous system infections.

The treatment of gram-negative infection of the central nervous system (CNS) presents a clinical challenge due to antibiotic resistance and difficulties with penetration into the cerebrospinal fluid (CSF). Two patients with gram-negative CNS infections were treated successfully with high-dose, prolonged infusions of meropenem. The CSF meropenem concentrations exceeded the minimum inhibitory concentration of the pathogen for virtually the entire dosing interval in both cases.

Differential efficacy of clarithromycin in lung versus thigh infection models.

Background: Differences in clarithromycin disposition and the resulting changes in bacterial density were studied using mouse lung and thigh infection models.

Methods: Clarithromycin activity was evaluated against seven Streptococcus pneumoniae isolates with efflux-mediated resistance in both murine lung and thigh infection models. Intrapulmonary disposition of clarithromycin was also studied.

Efficacy of clarithromycin against Streptococcus pneumoniae expressing mef(A)-mediated resistance.

As a result of macrolide resistance rates of 25% for pneumococci in the US, the clinical use of this class as empirical therapy has been questioned. However, macrolides continue to be used with clinical success. Using an immunocompromised murine pneumonia model, this study evaluated in vivo efficacy of human simulated exposures of clarithromycin for 62 isolates of Streptococcus pneumoniae considered resistant by current methods of breakpoint determinations.

Pharmacoeconomic analysis of amphotericin B lipid complex versus liposomal amphotericin B in the treatment of fungal infections.

Background: Potential differences in toxicity, potency and acquisition price among the liposomal amphotericin B formulations makes it unclear which agent is less costly when total resource consumption and treatment-associated costs are considered.

Design: A retrospective cost-minimisation analysis in 51 patients was performed to compare the cost of amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AMB) from the hospital perspective. Costs ($US, 2001 values) were divided into level I (acquisition price only), level II (costs of all associated treatment, i.

Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults.

Study Objective: To determine the steady-state, extracellular, and intracellular pulmonary disposition of moxifloxacin (MXF), levofloxacin (LEVO), and azithromycin (AZI) relative to that of the plasma over a 24-h dosing interval.

Design: Randomized, multicenter, open-label investigation.

Patients: Forty-seven older adults (mean [+/- SD] age, 62 +/- 13 years) undergoing diagnostic bronchoscopy.

Bactericidal effect of cethromycin (ABT-773) in an immunocompetent murine pneumococcal pneumonia model.

The efficacy of cethromycin was assessed against isolates of Streptococcus pneumoniae in the presence of neutrophils. Comparison with data from our previous neutropenic model revealed that the presence of neutrophils enhanced the bacteriostatic and bactericidal effect of cethromycin by an average of two- to four-times, respectively.

Measurement of adherence to antiretroviral medications.

Measurement of adherence may be important in determining why patients fail antiretroviral therapy. Although patient self-report is by far the most frequently used means of assessing adherence, it overestimates adherence. However, patients who state they are nonadherent almost always are.

Cost effect of managing methicillin-resistant Staphylococcus aureus in a long-term care facility.

Objectives: The purpose of this study was to measure the total consumption of resources involved in the care of a long-term care facility (LTCF) resident infected with methicillin-resistant Staphylococcus aureus (MRSA).

Design: A retrospective cohort study.

Setting: A 375-bed LTCF that provides two levels of care.

Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus pneumoniae in a murine neutropenic thigh infection model.

The objective of this study was to determine the susceptibility breakpoint of a new carbapenem, ertapenem (MK-0826), against Streptococcus pneumoniae strains based on bacterial density and survival studies in a murine thigh infection model. Sixteen S. pneumoniae isolates for which MICs ranged from 0.