A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila.

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

Effect of quinupristin/dalfopristin alone or in combination with vancomycin on the structure of Enterococcus faecium.

Twenty strains of Enterococcus faecium susceptible to quinupristin/dalfopristin (< 2 mg/l) were DNA fingerprinted to exclude strain duplication. Ten strains were susceptible to vancomycin (minimal inhibitory concentration [MIC] < 2 mg/l) and 10 were resistant to vancomycin (MIC > 400 mg/l). Vancomycin at 1/2 MIC, quinupristin/dalfopristin at 1/4 MIC and their combination, except for a tube control, was added to 10 ml trypticase soy broth tubes which were planted with the respective 24-h trypticase soy broth cultures. The products of incubation were sampled periodically throughout 24 h for gram stain and electron microscopy. Cell size was measured on photographs at 20,000x final magnification and results were statistically analyzed. The cells of all strains of Enterococcus faecium exposed for 12 h to quinupristin/dalfopristin were comparable in size to the control, Most cells, however, showed areas of low density of ribosome in the center of the cells. The cells of Enterococcus faecium resistant to vancomycin exposed to vancomycin were larger than the controls with means of 1.96 micron -2.07 micron versus 1.16 micron (p < 0.001); these cells consisted of individual organisms connected by wide cross walls of abnormal fibrous structure. Enterococcus faecium sensitive to vancomycin exposed to vancomycin remained comparable to the control. The combination of quinupristin/dalfopristin plus vancomycin produced large cells with multiple abnormal cross walls in both vancomycin-resistant and vancomycin-sensitive Enterococcus faecium. The addition of quinupristin/dalfopristin to vancomycin appears to modify the vancomycin-susceptible strains to respond to vancomycin in the same manner as do the vancomycin-resistant organisms.

Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Synergic activity of vancomycin-quinupristin/dalfopristin combination against Enterococcus faecium.

Clinical specimens were cultured, and the strains identified by the Vitek system as Enterococcus faecium were characterized by their DNA. The MIC vancomycin, quinupristin/dalfopristin and teicoplanin for each isolate was determined. Ten vancomycin-sensitive and ten vancomycin-resistant strains of E. faecium were tested. Quinupristin/dalfopristin at 0.25 x MIC and vancomycin at 0.5 x MIC separately as well as in combination were added to Trypticase Soy Broth tubes inoculated with a 24 h culture. The results obtained by determining cfu at 2, 4, 8, 12 and 24 h indicated that the combination of subinhibitory concentrations of quinupristin/dalfopristin plus vancomycin produced after 24 h, in vancomycin-resistant strains, a consistent degree of synergy. Synergy was observed up to only 12 h when similar combinations were employed for vancomycin-sensitive strains. Vancomycin-sensitive strains tended to be slightly less susceptible to quinupristin/dalfopristin than vancomycin-resistant strains.

Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Trends in the prevalence of methicillin-resistant Staphylococcus aureus associated with discontinuation of an isolation policy.

The number of patients with methicillin-resistant Staphylococcus aureus (MRSA) before and after discontinuing placement of patients into private rooms was determined. The mean monthly number of patients with MRSA decreased from 34 to 22, and the proportion of S aureus isolates that were MRSA decreased from 34% to 20%. We found no evidence that failure to isolate patients with MRSA resulted in an increased prevalence of MRSA.

The need for surveillance for antimicrobial resistance.

Currently, collection of bacterial susceptibility data is very incomplete; national or international susceptibility data simply do not exist. The large volume of scientific publications on this subject contributes to the perception that bacterial resistance to antimicrobials is extensive and growing. However, only a very few papers address the epidemiology of bacterial resistance. Those papers that do report quantitatively on this topic are from hospitals that are systematically different from hospitals that do not publish. No one can deny the existence and the importance of drug resistance, but the sensational reports from the media are grossly untrue. Multidrug-resistant bacteria affect an extremely small proportion of patients. Most antibiotics still are highly effective and cure the majority of infections. It is proposed that medical microbiology laboratories report their susceptibility data on eight common species that constitute 68.5% of all isolates. Such reports could be analyzed and published yearly.

RP 59500 postantibiotic effect defined by bacterial ultrastructure.

Staphylococcus aureus was exposed to 0.3 microgram/ml RP 59500, an injectable streptogramin, 0.75 minimum inhibitory concentration (MIC) for six hours, washed, resuspended in fresh medium and incubated for ten hours. The postantibiotic effect (PAE) was determined by growth kinetics and by bacterial ultrastructure. The PAE was eight hours when determined by changes in the cell diameters and three hours when determined by the count of colony forming units (CFU).

Oral ciprofloxacin versus intravenous therapy with other non-quinolone agents: a study of 291 infections.

A retrospective comparison of oral ciprofloxacin in mono- or combination therapy versus standard intravenous (i.v.) therapy with non-quinolone agents was undertaken to evaluate efficacy and cost in actual clinical practice. The choice, dose and duration of antibiotic therapy was determined solely by the patients' physicians. The patients were treated for infections of the lower respiratory tract; urinary tract and skin (totalling 291 infections). The most frequent species isolated were Escherichia coli (21.6%), Staphylococcus aureus (12%), and Pseudomonas aeruginosa (11.7%). No significant differences (p > 0.10) in the cure rates and duration of infection were observed when comparing oral ciprofloxacin only, versus standard i.v. therapy. The administration of simultaneous combination therapy resulted in a lower cure rate and longer infection, regardless of the site of infection. The duration of therapy required to show a cure or improvement was significantly shorter (p < 0.0001) for oral ciprofloxacin alone, than for i.v. therapy and ciprofloxacin combination therapies.

Medical relevance of low concentrations of antibiotics.

Low concentrations of antibiotics or sub-minimum inhibitory concentrations (sub-MIC) have been shown in vitro to alter the ultrastructure and antigenicity of bacteria, their adherence to epithelial cells, their synthesis and excretion of pathogenic enzymes and their rate of growth. The same effects have been detected when low concentrations of antibiotic act on bacteria in vivo. Animal experiments as well as clinical investigations have demonstrated therapeutic results with sub-MICs at the site of infection.

Effects of chlorpromazine on the cell envelope proteins of Escherichia coli.

Chlorpromazine (CPZ), at a concentration of 60 micrograms/ml of medium completely inhibited the replication of Escherichia coli. At concentrations below this MIC, CPZ caused transient induction of filamentation, such that by the end of 5 h, all of the cells were filaments, and by the end of 24 h, only rod-shaped E. coli were present. The reversion to normal morphology in the presence of CPZ was not due to either the degradation of CPZ or the selection of CPZ-resistant mutants. The electrophoretic pattern of proteins extracted from isolated cell envelopes of CPZ-induced filaments as well as from E. coli that reverted to normal morphology was distinctly different from that of the controls.

Predictive value of susceptibility tests for the outcome of antibacterial therapy.

A total of 510 charts of patients who received antibacterial agents were examined for clinical outcome and microbiology findings. A total of 382 patients (75%) had one or more specimens submitted for culture and susceptibility tests before the administration of the drugs; 298 (78%) of these had positive cultures and susceptibility tests were done. A total of 18 species were isolated. Of the 298 patients with organisms of known susceptibilities, 271 (91%) received antibacterial agents to which the respective organisms were susceptible and 219 of these patients (81%) improved (P less than 0.05). This high rate of good infectious diseases practice is probably due to two factors: (1) susceptibility tests results were available in most cases the next day after the submission of a specimen; (2) the medical board distributed guidelines for the use of antibiotics and monitored the compliance closely. The patients treated with antibacterial agents to which the bacteria were resistant improved in 3% and did not improve in 82% (P less than 0.05) of the patients. This study shows that choosing an antibacterial agent in accordance to the susceptibility test resulted in a high rate of improvement. When the choice of agent disregarded bacterial resistance in vitro, therapy almost always ended in failure. Therefore, susceptibility tests in vitro have a good predictive value for the outcome of antibacterial therapy.