Dalfopristin

About: Dalfopristin is a research topic. Over the lifetime, 696 publications have been published within this topic receiving 26621 citations. The topic is also known as: RP-54476 & Dalfopristina.

Sequential regimen for early post-surgical infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA), unresponsive to standard antibiotic therapy: a case report.

Abstract: We describe a patient with early post-surgical infective endocarditis due to methicillin-resistant Staphylococcus aureus, who was unsuitable for surgical reintervention and who failed standard antistaphylococcal therapy, but was successfully cured with a sequential regimen including quinupristin/dalfopristin and linezolid.

Relatively high rates of cefotaxime- and ceftriaxone-non-susceptible isolates among group B streptococci with reduced penicillin susceptibility (PRGBS) in Japan

Abstract: OBJECTIVES We have previously identified group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) that were non-susceptible to cefotaxime; however, the rates of cefotaxime and ceftriaxone non-susceptibility among PRGBS isolates have never been reported. Therefore, we first determined the MICs of 22 antibacterial drugs/compounds for 74 PRGBS isolates and then determined the rates of cefotaxime and ceftriaxone non-susceptibility among these isolates. METHODS We used 74 clinical PRGBS isolates, previously collected in Japan and confirmed to harbour relevant amino acid substitutions in PBP2X. We also used 80 penicillin-susceptible GBS (PSGBS) clinical isolates as controls. The MICs of 22 antibacterial drugs/compounds for all 154 GBS isolates were determined via microdilution and/or agar dilution methods, as recommended by the CLSI. RESULTS The rates of non-susceptibility/resistance to ampicillin, cefotaxime, ceftriaxone and levofloxacin for the 80 PSGBS isolates were 0%, 0%, 0% and 30%, respectively, but were 15% (P = 0.0003), 28% (P < 0.0001), 36% (P < 0.0001) and 93% (P < 0.0001) for the 74 PRGBS isolates, respectively. No PRGBS isolates were identified to be non-susceptible to meropenem, doripenem, vancomycin, quinupristin/dalfopristin, daptomycin or linezolid. CONCLUSIONS We found that cefotaxime- and ceftriaxone-non-susceptible PRGBS isolates occur at relatively high rates in Japan. Importantly, this finding suggests that the range of drugs likely to be effective in treating PRGBS infections may be limited compared with those available for PSGBS infections; therefore, clinicians should exercise care when considering drug choice and efficacy for PRGBS infections.

Quinupristin-Dalfopristin Is Active against Toxoplasma gondii

Abstract: Synercid and each of its components (quinupristin and dalfopristin) were examined for their activities against Toxoplasma gondii. In vitro, intracellular replication of tachyzoites was inhibited by synercid and each of its two components. The 50% inhibitory concentrations of synercid, quinupristin, and dalfopristin were 1.6, 2.7, and 6.3 microg/ml, respectively. Thus, synercid was markedly more active than its components. Treatment of acutely infected mice with 100 or 200 mg of synercid per kg of body weight per day administered intraperitoneally for 10 days resulted in survival of 50% (P = 0.0002) and 100% (P < 0.0001) of infected mice, respectively, whereas all control mice died by day 18. In contrast, treatment with 200 mg of either quinupristin and dalfopristin per kg per day alone resulted in only 20% survival; treatment with 50 mg of either drug per kg per day resulted only in the prolongation of time to death. These results suggest that synercid may be useful for treatment of toxoplasmosis in humans.

Potential for Reduction of Streptogramin A Resistance Revealed by Structural Analysis of Acetyltransferase VatA

Abstract: Combinations of group A and B streptogramins (i.e., dalfopristin and quinupristin) are “last-resort” antibiotics for the treatment of infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Resistance to streptogramins has arisen via multiple mechanisms, including the deactivation of the group A component by the large family of virginiamycin O-acetyltransferase (Vat) enzymes. Despite the structural elucidation performed for the VatD acetyltransferase, which provided a general molecular framework for activity, a detailed characterization of the essential catalytic and antibiotic substrate-binding determinants in Vat enzymes is still lacking. We have determined the crystal structure of S. aureus VatA in apo, virginiamycin M1- and acetyl-coenzyme A (CoA)-bound forms and provide an extensive mutagenesis and functional analysis of the structural determinants required for catalysis and streptogramin A recognition. Based on an updated genomic survey across the Vat enzyme family, we identified key conserved residues critical for VatA activity that are not part of the O-acetylation catalytic apparatus. Exploiting such constraints of the Vat active site may lead to the development of streptogramin A compounds that evade inactivation by Vat enzymes while retaining binding to their ribosomal target.

Microbiologic characteristics of pathogenic bacteria from hospitalized trauma patients who survived Wenchuan earthquake.

Abstract: The purpose of this study is to investigate the microbiological characterization of pathogenic bacteria isolated from trauma patients after Wenchuan earthquake in 2008. Most infections were identified in the patients over 60 years of age, with an incidence rate of 78.5%, and more infections in wound (43.3%) and respiratory tract (37.1%) sites were identified. A total of 97 non-duplicated clinical pathogens were isolated from 91 trauma patients. Of those pathogens, 62 (63.9%) were Gram-negative bacilli, 23 (23.7%) were Gram-positive cocci, 9 (9.3%) were fungi, and 3 (3.1%) were anaerobes, such as Clostridium perfringens. The distribution spectrum of pathogens isolated from trauma patients after earthquake was different to that from non-earthquake trauma patients in our hospital at the same time. The most prevalent pathogenic isolates were Escherichia coli (15.4%), Acinetobacter baumannii (14.4%), Staphylococcus aureus (12.3%), Burkholderia cepacia (11.3%), and Enterococcus spp. (9.3%). The drug susceptibility results showed that most of the Gram-negative bacilli, except for Pseudomonas aeruginosa and Burkholderia cepacia, were susceptible to imipenem, but resistant to the first- and the second-generation cephalosporins. Most of the Gram-positive cocci were susceptible to vancomycin, linezolid, and Synercid/dalfopristin. Characteristics of pathogenic bacterium isolated from trauma patients after earthquake have been demonstrated which play an important role in the appropriate treatment of infections.