Medline ® Abstracts for References 52-54

of 'Treatment of community-acquired pneumonia in adults who require hospitalization'

52
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Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
AU
Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE
SO
J Infect Dis. 2007;195(2):202.
 
Extracellular protein toxins contribute to the pathogenesis of a wide variety of Staphylococcus aureus infections. The present study investigated the effects that cell-wall active antibiotics and protein-synthesis inhibitors have on transcription and translation of genes for Panton-Valentine leukocidin, alpha-hemolysin, and toxic-shock syndrome toxin 1, in both methicillin-sensitive and methicillin-resistant S. aureus. Subinhibitory concentrations of nafcillin induced and prolonged mRNA for Panton-Valentine leukocidin, alpha-toxin, and toxic-shock syndrome toxin 1 and increased toxin production. In contrast, clindamycin and linezolid markedly suppressed translation, but not transcription, of toxin genes. These results suggest (1) that protein-synthesis inhibition is an important consideration in the selection of antimicrobial agents to treat serious infections caused by toxin-producing gram-positive pathogens and (2) that, by inducing and enhancing toxin production, inadvertent use of beta-lactam antibiotics to treat methicillin-resistant S. aureus infections may contribute to worse outcomes.
AD
Veterans Affairs Medical Center, Boise, ID 83702, USA. dlsteven@mindspring.com
PMID
53
TI
Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator.
AU
Vesga O, Agudelo M, Salazar BE, Rodriguez CA, Zuluaga AF
SO
Antimicrob Agents Chemother. 2010;54(8):3271.
 
Generic versions of intravenous antibiotics are not required to demonstrate therapeutic equivalence with the innovator because therapeutic equivalence is assumed from pharmaceutical equivalence. To test such assumptions, we studied three generic versions of vancomycin in simultaneous experiments with the innovator and determined the concentration and potency of the active pharmaceutical ingredient by microbiological assay, single-dose pharmacokinetics in infected mice, antibacterial effect by broth microdilution and time-kill curves (TKC), and pharmacodynamics against two wild-type strains of Staphylococcus aureus by using the neutropenic mouse thigh infection model. The main outcome measure was the comparison of magnitudes and patterns of in vivo efficacy between generic products and the innovator. Except for one product exhibiting slightly greater concentration, vancomycin generics were undistinguishable from the innovator based on concentration and potency, protein binding, in vitro antibacterial effect determined by minimal inhibitory or bactericidal concentrations and TKC, and serum pharmacokinetics. Despite such similarities, all generic products failed in vivo to kill S. aureus, while the innovator displayed the expected bactericidal efficacy: maximum antibacterial effect (Emax) (95% confidence interval [CI]) was 2.04 (1.89 to 2.19), 2.59 (2.21 to 2.98), and 3.48 (2.92 to 4.04) versus 5.65 (5.52 to 5.78) log10 CFU/g for three generics and the innovator product, respectively (P<0.0001, any comparison). Nonlinear regression analysis suggests that generic versions of vancomycin contain inhibitory and stimulatory principles within their formulations that cause agonistic-antagonistic actions responsible for in vivo failure. In conclusion, pharmaceutical equivalence does not imply therapeutic equivalence for vancomycin.
AD
GRIPE (Grupo Investigador de Problemas en Enfermedades Infecciosas), Calle 62 No. 52-59, Lab. 630, SIU, UdeA, MedellĂ­n, Colombia. omar.vesga@siu.udea.edu.co
PMID
54
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Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season.
AU
Kallen AJ, Brunkard J, Moore Z, Budge P, Arnold KE, Fosheim G, Finelli L, Beekmann SE, Polgreen PM, Gorwitz R, Hageman J
SO
Ann Emerg Med. 2009;53(3):358.
 
STUDY OBJECTIVE: Staphylococcus aureus is a cause of community-acquired pneumonia that can follow influenza infection. In response to a number of cases reported to public health authorities in early 2007, additional case reports were solicited nationwide to better define S. aureus community-acquired pneumonia during the 2006 to 2007 influenza season.
METHODS: Cases were defined as primary community-acquired pneumonia caused by S. aureus occurring between November 1, 2006, and April 30, 2007. Case finding was conducted through an Emerging Infections Network survey and through contacts with state and local health departments.
RESULTS: Overall, 51 cases were reported from 19 states; 37 (79%) of 47 with known susceptibilities involved infection with methicillin-resistant S. aureus (MRSA). The median age of case patients was 16 years, and 44% had no known pertinent medical history. Twenty-two (47%) of 47 case patients with information about other illnesses were diagnosed with a concurrent or antecedent viral infection during their illness, and 11 of 33 (33%) who were tested had laboratory-confirmed influenza. Of the 37 patients with MRSA infection, 16 (43%) were empirically treated with antimicrobial agents recommended for MRSA community-acquired pneumonia. Twenty-four (51%) of 47 patients for whom final disposition was known died a median of 4 days after symptom onset.
CONCLUSION: S. aureus continues to cause community-acquired pneumonia, with most reported cases caused by MRSA and many occurring with or after influenza. In this series, patients were often otherwise healthy young people and mortality rates were high. Further prospective investigation is warranted to clarify infection incidence, risk factors, and preventive measures.
AD
Division of Healthcare Quality Promotion, National Center for Preparedness, Detection and Control of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. AKallen@cdc.gov
PMID