SUMMARYEthidium bromide, a trypanocidal drug affecting nucleic acid synthesis, was found to be a powerful agent in eliminating some antibiotic resistance in bacteria. In staphylococci, penicillinase production was eliminated in mercury-resistant organisms, but not in mercury-sensitive ones. Among enterobacteria, two resistance factors showing the same resistance pattern were differently eliminated, and correlation between elimination and transfer of resistance factors was not always observed. F'-lac+ factor was also eliminated by ethidium bromide in Escherichia coli ~1 2 .Elimination of antibiotic resistance was observed generally at high frequency, and could be better reproduced than with acridine dyes.
Salmonella enterica serotype Typhi clinical isolates (n ؍ 91) resistant to nalidixic acid (Nal r ) were collected from sporadic cases and minor outbreaks throughout Vietnam between 1996 and 2004. These isolates were typed and compared by four methods: Vi phage typing, PstI ribotyping, XbaI and SpeI pulsed-field gel electrophoresis (PFGE), and single-nucleotide polymorphism (SNP) analysis. The results indicated that 65% of the isolates were not typeable by Vi phage typing. In contrast, the ribotyping and, with more accuracy, the SNP analysis methods indicated that all Nal r isolates belonged to a single clone (ribotype 3a, haplotype H58) that was found previously and that largely consisted of plasmid-encoded multidrug-resistant serotype Typhi isolates. PFGE demonstrated the occurrence of microevolution within this clone. We identified two major combined PFGE profiles: X1-S1 and X3-S6. X3-S6 predominated between 1996 and 2002 but was replaced by X1-S1 after 2002. Nevertheless, PFGE, with a Simpson's index of 0.78, was not considered an optimal discriminatory method for investigating typhoid fever outbreaks in Vietnam. The rate of quinolone resistance increased and the rate of multidrug resistance decreased during the study period. From 2002 to 2004, 80.6% of the isolates from South Vietnam were resistant only to Nal. The mechanism of Nal resistance in most of the isolates (94%) was a mutation in the quinolone resistance-determining chromosomal region of gyrA that led to the amino acid substitution Ser83Phe. No plasmid-located qnrA, qnrB, or qnrS was detected.
Amoxicillin, cefotaxime, ceftriaxone, gentamicin, doxycycline, and ofloxacin were active in vitro, like the reference drug streptomycin, against the virulent strain Yersinia pestis 6/69M. The comparative efficacies of these drugs in vivo were evaluated in a standardized and reproducible mouse model of systemic infection. Each antibiotic was injected intravenously once, at 24 h postinfection, and then repeatedly during 48 h. In vivo results were measured by counting the viable bacteria recovered from the whole spleens of mice sacrificed at selected times. All the drugs were manifestly successful; ceftriaxone, ofloxacine, and the reference drug were the most effective. Therefore, gentamicin and doxycycline could be used, depending on the clinical forms of the Y. pestis infection. Further investigations on beta-lactams, especially those used in the present study, could be carried out to confirm or not confirm their activities against Y. pestis. Ofloxacin appeared to be as active and to perform as rapidly as streptomycin in the treatment of murine Y. pestis infection, which is in agreement with the previous successes obtained with the use of fluoroquinolones in the treatment of murine infections caused by other pathogenic yersiniae.Three pathogenic species are included in the genus Yersinia. Y enterocolitica and Y pseudotuberculosis essentially cause gastroenteritis and occasionally septicemia. Y pestis, which was discovered in 1894 by Alexandre Yersin, is the agent of plague.Despite the efforts of public health workers to control plague, this infection still has a widespread distribution in the world (7,20,22,25,35). During the last decade (1980 to 1989), 21 countries notified the World Health Organization of almost 10,000 cases of plague, and the global fatality rate was 11.5%, with peaks in some countries exceeding 35% (35). If, at the moment, the worldwide incidence seems to be stable, a few countries regularly report an increasing number of cases. In the four past decades (the 1950s, 1960s, 1970s, and 1980s), the United States has recorded 10, 28, 105, and 179 cases of plague, respectively (6, 35). Septicemic plague, which is difficult to recognize, may represent 20 to 25% of the cases of plague in the United States (17, 34). Secondary localizations, for example, pulmonary or meningeal, may complicate 6% of cases of bubonic or septicemic plague (3, 5) and up to now have been characterized by a high death rate, in some reports rising to 33% (2, 17).Forty years ago, Meyer (23) considered streptomycin, chloramphenicol, and tetracyclines to be reference drugs for the treatment of plague, and they are still recommended for that use today (3). This limited antibiotic choice can be a serious handicap because of (i) localization of the disease (e.g., meningitis), (ii) underlying disease, or (iii) antibiotic side effects.In the face of this dilemma, it seemed to us that it would be useful to evaluate the in vivo comparative efficacies of newer antibiotics like fluoroquinolones and extended-spectrum cephalosporins agains...
Of 53 documented cases of Yersinia enterocolitica septicemia reported to the French national registry between 1985 and 1991, 43 files contained sufficient information on antibiotic treatment to be analyzed retrospectively. All patients had at least two positive cultures of blood collected before the initiation of treatment. All strains were susceptible in vitro to the antibiotics that are usually active against gram-negative rods except for older beta-lactam agents (i.e., aminopenicillins and first-generation cephalosporins). No multiresistant strain was isolated. Only four (7.5%) of the 53 patients died. Aminopenicillins, first-generation cephalosporins, and--when prescribed alone--amoxicillin/clavulanate were not effective. Third-generation cephalosporins, most often used in combination with other antibiotics, were successful in 85% of cases. Fluoroquinolones--alone or in combination--cured all of 15 infections, with patients improving rapidly and becoming apyretic within 1-4 days. These agents therefore seem to constitute the best treatment.
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