Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Aug 2014
Population-based cohort study of anti-infective medication use before and after the onset of type 1 diabetes in children and adolescents.
A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of anti-infective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescriptions (1999 to 2009) were identified (T1D cohort) and compared with an age- and sex-matched (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average number of anti-infective use was studied from (up to) 8 years before until a maximum of 4 years after the onset of T1D. ⋯ This pattern was consistent across sex and age categories and already observed in the year before the onset of type 1 diabetes. Patients in the T1D cohort received more antibacterials (49.8 compared to 40%, P < 0.001), antimycotics (4.0 compared to 1.3%, P < 0.001), antivirals (2.5 compared to 0.4%, P < 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems. Our findings that elevated anti-infective use in the T1D cohort exists in the period before the onset of type 1 diabetes and the consumption of more second-line anti-infective compounds in this time period warrant further research.
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Antimicrob. Agents Chemother. · Aug 2014
Alternative screening approaches for discovery of Middle East respiratory syndrome coronavirus inhibitors.
Two coronaviruses causing severe respiratory disease and high mortality rates emerging within the past dozen years reinforces the need for clinically efficacious antivirals targeting coronaviruses. Alternative screening approaches for antivirals against the recently emergent Middle East respiratory syndrome coronavirus (MERS-CoV) may provide lead compounds to address this need. Two Antimicrobial Agents and Chemotherapy (AAC) papers screened libraries of approved compounds that may potentially be repurposed as MERS-CoV antivirals. A third AAC paper showed that a previously described severe acute respiratory syndrome coronavirus (SARS-CoV) helicase inhibitor also has activity against MERS-CoV.
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Antimicrob. Agents Chemother. · Aug 2014
A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models.
Pseudomonas aeruginosa is a major cause of hospital-acquired infections, particularly in mechanically ventilated patients, and it is the leading cause of death in cystic fibrosis patients. A key virulence factor associated with disease severity is the P. aeruginosa type III secretion system (T3SS), which injects bacterial toxins directly into the cytoplasm of host cells. The PcrV protein, located at the tip of the T3SS injectisome complex, is required for T3SS function and is a well-validated target in animal models of immunoprophylactic strategies targeting P. aeruginosa. ⋯ V2L2MD, while not the most potent MAb as assessed by in vitro cytotoxicity inhibition assays, provided strong prophylactic protection in several murine infection models and a postinfection therapeutic model. V2L2MD mediated significantly (P < 0.0001) better in vivo protection than that provided by a comparator antibody, MAb166, a well-characterized anti-PcrV MAb and the progenitor of a clinical candidate, KB001-A. The results described here support further development of a V2L2MD-containing immunotherapeutic and may suggest even greater potential than was previously recognized for the prevention and treatment of P. aeruginosa infections in high-risk populations.
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Antimicrob. Agents Chemother. · Jul 2014
Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia.
The time to antibiotic administration (TTA) has been proposed as a quality-of-care measure in febrile neutropenia (FN); however, few data regarding the impact of the TTA on the mortality of adult cancer patients with FN are available. The objective of this study was to determine whether the TTA is a predictor of mortality in adult cancer patients with FN. A prospective cohort study of all consecutive cases of FN, evaluated from October 2009 to August 2011, at a single tertiary referral hospital in southern Brazil was performed. ⋯ Early antibiotic administration was associated with higher survival rates in the context of FN. Efforts should be made to ensure that FN patients receive effective antibiotic therapy as soon as possible. A target of 30 min to the TTA should be adopted for cancer patients with FN.
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Antimicrob. Agents Chemother. · Jul 2014
Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy.
Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. ⋯ Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r(2) of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.