Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 g/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 g/ml for the three strains. Reduction of log 10 CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (⌬lung counts: ؊5.38 and ؊4.64 log 10 CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (؊4.16 and ؊5.15 log 10 CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (؊2.39 log 10 CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic-and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: ؊1.24, ؊2.26, ؊2.1, ؊1.56, ؊1.47, ؊1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P ‫؍‬ 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r ‫؍‬ 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.Patients suffering from orthopedic device infections will have usually undergone surgical interventions and received antibiotic therapies over a long period of time, these being major clinical issues. It is very difficult to eradicate such infections using antibiotics because of the formation of biofilm, a protein matrix including bacteria with reduced metabolism and with tolerance to antimicrobials (2,9,11,38).These infections are frequently caused by Staphylococcus aureus, and rifampin has been shown to be the most effective antimicrobial agent in such cases, in in vitro and experimental studies (26, 48) and in clinical practice (14,15,46). Since this drug should not be given alone due to the development of early bacterial resistance, antibiotic combinations are required. The combination of rifampin and fluoroquinolones has been found to be particularly efficacious and is thus usually recommended (10,14,44).In recent years, the experimental foreign-body infection model developed by Lucet et al. (26) has provided relevant data regarding the antimicrobial efficacy of several antibiotics ...

Rupatadine oral solution (1 mg/ml) was significantly more effective than placebo in reducing nasal symptoms at 4 and 6 wk and was well tolerated overall. This is the first large clinical report on the efficacy of an H1 receptor antagonist in children with PER in both symptoms and quality of life.

The most frequent symptoms reported by women diagnosed with uterine myomas were heavy menstrual bleeding, pelvic or abdominal pain and dysmenorrhea; QoL was impaired reflecting high symptom distress. We found that surgery was the main therapeutic approach to manage uterine myomas in Spain. Both surgical and non-surgical treatments achieve relevant improvements in symptom severity and quality of life.