virginiamycin and Pneumonia--Pneumococcal

During the last decade there has been an unexpectedly rapid evolution of antimicrobial resistance in the respiratory pathogens for community- and hospital-acquired pneumonia. In order to choose the most optimal therapy for their patients, it is essential that physicians be aware of the prevalence and mechanisms of resistance and their implications on the effectiveness of the various antimicrobials.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; DNA Topoisomerases, Type II; Drug Resistance, Microbial; Drug Resistance, Multiple; Genes, Bacterial; Gram-Negative Bacterial Infections; Gram-Negative Facultatively Anaerobic Rods; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Mutation; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Staphylococcus aureus; Streptococcus pneumoniae; Virginiamycin

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Topics: Adult; Aged; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Prospective Studies; Treatment Outcome; Vancomycin; Virginiamycin

Resistance to quinupristin-dalfopristin (Q/D) among gram-positive cocci has been very uncommon. Two clinical isolates among 8,837 (0.02%) Streptococcus pneumoniae isolates were discovered in 2001 to 2002 with Q/D MICs of 4 micro g/ml. Each had a 5-amino-acid tandem duplication (RTAHI) in the L22 ribosomal protein gene (rplV) preventing synergistic ribosomal binding of the streptogramin combination. Similar gene duplication has been reported in Q/D-resistant Staphylococcus aureus.

Topics: Anti-Bacterial Agents; Base Sequence; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Molecular Sequence Data; Mutation; Pneumonia, Pneumococcal; Population Surveillance; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins; RNA-Binding Proteins; Streptococcus pneumoniae; United Kingdom; Virginiamycin

We report a failure of pristinamycin treatment in a case of pneumonia caused by streptogramins B-type resistant pneumococcus. We suggest that (i) streptogramins therapy should be avoided, if a previous treatment failure has been observed with a macrolide and/or if the antibiogram shows the MLS(B) co-resistance phenotype, and (ii) beta-lactams should remain the first-line antibiotics used for treatment of pneumococcal respiratory infections.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Microbial; Female; Humans; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Failure; Virginiamycin

A case of pneumonia caused by Streptococcus pneumoniae occurring in a patient receiving pristinamycin is reported. Despite empirical treatment with pristinamycin, 2 g/day for five days, the patient's condition worsened. Protected brush specimen and blood cultures permitted isolation of Streptococcus pneumoniae. MIC testing indicated that the strain was susceptible to pristinamycin and resistant to erythromycin and penicillin. Streptococcus pneumoniae was eradicated by cefotaxime, and pneumonia resolved. This case underlines the fact that pristinamycin may not be suitable for the treatment of multiresistant pneumococcal infections.

Topics: Aged; Drug Resistance, Microbial; Drug Resistance, Multiple; Female; Humans; Microbial Sensitivity Tests; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Failure; Virginiamycin