Treatment of experimental endocarditis due to multidrug-resistant Enterococcus faecium with clinafloxacin and penicillin

OBJECTIVE: To determine the influence of sperm morphology and the number of motile sperm inseminated on the outcome of IUI in hMG-stimulated cycles and to establish lower limits for these variables below which the expectation of pregnancy is limited. DESIGN: Retrospective study of data from 1990 to 1992. SETTING: Tertiary referral Reproductive Medicine Unit. Patients: Couples with bilaterally patent fallopian tubes, and > or = 200,000 motile sperm recovered in a trial preparation before treatment. No other semen criteria were used to exclude couples. Women were stimulated with hMG irrespective of whether they were ovulatory or anovulatory. The study comprised 163 couples who underwent 330 cycles. MAIN OUTCOME MEASURES: Pregnancy rate (PR) per cycle was related to the percentage normal sperm morphology in the fresh semen sample and the number of motile sperm inseminated after sperm preparation by swim-up or Percoll gradients. RESULTS: The overall PR was 16.1% per cycle. The PR was highest in the first cycle of treatment (21.4%) and declined in the second and third cycles. The miscarriage rate was 10.4% and the incidence of multiple pregnancies was 13.9%. Two groups of patients were defined on the basis of sperm morphology: a "poor outcome" group ( < or = 10% normal) and a "good outcome" group ( > 10% normal). The PRs in these two groups were 4.3% and 18.2%, respectively, and the cumulative PRs after three cycles were 8.3% and 40.1%, respectively. The number of motile sperm inseminated did not significantly affect the PR. CONCLUSIONS: The degree of teratozoospermia affected the PR in hMG-stimulated IUI cycles and a normal morphology value of 10% in the fresh semen distinguished couples with good and poor outcomes. In contrast, the number of motile sperm inseminated did not significantly influence IUI outcome.     

Successful treatment with ampicillin and fluoroquinolones of human endocarditis due to high-level gentamicin-resistant enterococci

Two cases of endocarditis, one caused by high-level gentamicin-resistant Enterococcus durans and the other by high-level gentamicin- and glycopeptide-resistant Enterococcus faecalis. successfully treated with a combination of ampicillin and a fluoroquinolone are reported. Both strains were susceptible to ampicillin. Enterococcus faecalis was susceptible to ciprofloxacin and to ofloxacin, but Enterococcus durans was moderately resistant to these agents. Microbiological and clinical cure was obtained with a 6-week course of ampicillin plus ciprofloxacin in one case and with ofloxacin in the second case due to intolerance to ciprofloxacin. The efficacy of the treatment was predicted in vitro by time-kill studies and by adequate serum bactericidal titres.     

Critical importance of in vivo amoxicillin and cefotaxime concentrations for synergy in treatment of experimental Enterococcus faecalis endocarditis

Although a higher incidence of ectopic pregnancy has been reported after in-vitro fertilization (IVF) and embryo transfer, three ectopic pregnancies in the same woman is very rare. A patient of 32 years underwent IVF-embryo transfer six times within 3 years. Three of four conceptions resulted in ectopic pregnancies. The first involved simultaneous intrauterine and left tubal pregnancy, the second was a right tubal pregnancy, and the third was a right interstitial pregnancy. In IVF-embryo transfer, bilateral salpingectomy does not remove the risk of interstitial or cornual pregnancy.     

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.     

Efficacy of trovafloxacin, a new quinolone antibiotic, in experimental staphylococcal endocarditis due to oxacillin-resistant strains

Therapeutic options for severe infections caused by strains of oxacillin-resistant Staphylococcus aureus (ORSA) and coagulase-negative staphylococci (ORSE) are very limited. With the increasing resistance of such strains to aminoglycosides, rifampin, and currently available quinolone agents, as well as the recent documentation of increasing resistance of ORSA to vancomycin (VANCO), new treatment alternatives are imperative. The in vivo efficacy of trovafloxacin (TROVA), a new quinolone agent with excellent antistaphylococcal activity in vitro, against experimental endocarditis (IE) due to beta-lactamase-producing ORSA and ORSE strains (ORSA and ORSE IE) was evaluated. TROVA (25 mg/kg of body weight intravenously [i.v.] twice daily [b.i.d]) was compared to VANCO (20 mg/kg i.v. b.i.d.) and two regimens of ampicillin-sulbactam (AMP-SUL; 200 mg/kg intramuscularly [i.m.] three times a day [t.i.d.] and 20 mg/kg i.m. b.i.d.), with all agents given for 3 or 6 days. AMP-SUL was included as a comparative treatment regimen because of its proven efficacy against experimental ORSA and ORSE IE. For both ORSA and ORSE IE, TROVA, AMP-SUL, and VANCO each reduced staphylococcal densities in vegetations compared to untreated controls (P < 0.01). For ORSA IE, TROVA was the most rapidly bactericidal agent--although not to a statistically significant degree--correlating with its superior bactericidal effect in vitro compared to those of VANCO and AMP-SUL.     

Studies of protein binding to nonpolar solutes by using zonal elution and high-performance affinity chromatography: interactions of cis- and trans-clomiphene with human serum albumin in the presence of beta-cyclodextrin

High-performance affinity chromatography and zonal elution studies were used to examine the binding that takes place between the drug clomiphene and the protein human serum albumin (HSA). Equations were derived to describe the behavior of zonal elution experiments in which a solubilizing agent is present in the mobile phase to aid in the dissolution of a competing agent or injected analyte. These equations were then used to determine the association equilibrium constants for the clomiphene/HSA system, with beta-cyclodextrin being used as a complexation agent to improve the water solubility of cis- and trans-clomiphene without affecting the nature of their binding to HSA. It was found in these studies that both cis- and trans-clomiphene have 1:1 interactions at a common binding region on HSA (association constants at pH 7.4 and 37 degrees C: cis, 7.5 x 10(6) M-1; trans, 1.3 x 10(6) M-1). Further competition experiments between cis- or trans-clomiphene and various site-selective probes indicated that the clomiphene-binding region is the same as the proposed tamoxifen site of HSA. The approach and equations used within this report are general ones that can be applied to zonal elution studies of other solute-ligand systems in which one or more of the test components have limited solubility in the desired mobile phase.