Activity of macrolides, lincosamines, streptogramins and fluoroquinolones against streptococcus pneumoniae and enterococci isolates from the western hemisphere: example of international surveillance (SENTRY antimicrobial surveillance program )in the development of new drugs.
Resistance among commonly isolated Gram-positive cocci have compromised the available therapeutic regimens and require structured monitoring at the local, regional, national, and international levels. Two popular treatment classes of antimicrobials (macrolides-lincosamines-streptogramins [MLS], fluoroquinolones) have been tested against 3, 049 isolates of Streptococcus pneumoniae and enterococci from the SENTRY Antimicrobial Surveillance program. The strains were obtained from clinical cases in hospitals in the United States, Canada, and six nations (10 medical centers )in Latin America. MLS and fluoroquinolone compounds had moderate activity against vancomycin-susceptible Enterococcus faecalis only (gatifloxacin, and trovafloxacin MIC(50), 0.5 microg/ml), and quinupristin/dalfopristin was potent only against E.faecium isolates (MIC(90), 1 microg/ml(-2) microg/ml). When tested against pneumococci, gatifloxacin, trovafloxacin, sparfloxacin, and quinupristin/dalfopristin (MIC(90), or =99.8% and 84.7% to 99.1% of strains, respectively. These results from a global resistance monitoring program should encourage rapid drug development. Based on in vitro sensitivity testing, they indicate a promising role for the treatment of emerging resistant Gram-positive cocci. The clinical role for each new agent will depend on safety profiles, rates of administration, and other issues identified during development in the clinical trials process.
BACKGROUND: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. MATERIALS AND METHODS: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution. RESULTS: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p
The incidence of Neisseria gonorrhoeae with reduced susceptibility to quinolones increased from 0.18% (63 of 3285) in 1992 to 0.56% (15 of 2663) in 1993 and 0.62% (46 of 2846) in 1994. In all, 65 of the 67 isolates of Neisseria gonorrhoeae with decreased susceptibility to quinolones were characterised by pulsed-field gel electrophoresis (PFGE), auxotyping, serotyping and plasmid content. The strains were distributed among 14 auxotype/serovar (A/S) classes. Thirty isolates (46.2%) which were penicillin-susceptible with ciprofloxacin MIC90 of 0.12 mg/L and norfloxacin MIC90 of 1.0 mg/L belonged to a single A/S class, OUHL/IA-2. All but two of the 30 isolates had identical PFGE restriction profiles with NheI restriction endonuclease. Fifteen isolates (23.1%) with MICs in the intermediate (or resistant) categories for penicillin and with ciprofloxacin and norfloxacin MIC90 of 0.25 and 4.0 mg/L and (0.5 and 4.0 mg/L) respectively, belonged to A/S class P/IB-1. The 15 isolates showed nine different patterns with NheI and eight patterns with SpeI restriction endonucleases. Two of three beta-lactamase-producing (PPNG) isolates belonged to A/S class P/IB-5 and had a dissimilar PFGE restriction profile with NheI endonuclease; the other isolate belonged to A/S class P/IB-8. The remaining 17 isolates were distributed among 11 A/S classes. Three isolates within the common A/S class NR/IB-1 were subdivided into two types by PFGE as were three isolates belonging to A/S class NR/IB-2. Overall the 65 isolates of N. gonorrhoeae were distributed into 30 NheI and 26 SpeI macrorestriction profiles. All but one isolate harboured the 2.6-MDa cryptic plasmid and 18 isolates carried the 24.5-MDa transferable plasmid. The three PPNG isolates carried the 4.5-MDa Asian beta-lactamase-producing plasmid and a 25.2-MDa conjugative plasmid was found in the two TRNG isolates.
It is known that many pathogenic and toxic agents may attach to binding site of the same endogenic receptor. Such an effect is due to the resemblance between chemical structures in foreign agents. One may imagine the structure which contains binding-site fragments and may compete with the receptor for foreign agents. Then next suggestions are probable: (1)The same substance may interact with some agents with established resemblance; (2) If substance (1) interacts with agents A and B and substance (2) influences agent (2) only then (2) ought to act at agent B as well. In terms 'key-keyhole' this means an existence of the key fitting several keyholes. Application of this conception has given a possibility to predict an anti-HIV and antimicrobial activity of an antirabies immunoglobulin.
We describe a simple and standardised screening system (AREB) for surveillance of antibiotic resistant bacteria in the environment. The system consists of 96 well microplates containing eight sets of breakpoint amounts of 10 different antibiotics. The incubated microplates are read by a desktop scanner and the plate images are analysed by special software that automatically presents the resistance data. The AREB method is combined with a rapid typing method, the PhenePlate system, which yields information on the diversity of the bacteria in the studied samples, and on the possible prevalence of resistant clones. In order to demonstrate the usage of AREB, a comparative study on the resistance situation among 970 Escherichia coli isolates from sewage and recipient water in Sweden, Norway and Chile, was performed. Resistance rates to all antibiotics were markedly higher in hospital sewage than in other samples. Our data indicate that the AREB system is useful for comparing resistance rates among E. coli and other environmental indicator bacteria in different countries/regions. Simple handling and automatic data evaluation, combined with low cost, facilitate large studies involving several thousands of isolates.
A collection of 178 pneumococcal isolates found in Norway during the period 1987-1994 were tested for their susceptibility to benzylpenicillin, macrolides (azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin), fluoroquinolones (ciprofloxacin, sparfloxacin), imipenem, chloramphenicol, and vancomycin by a standard agar dilution procedure. To benzylpenicillin, two strains (1%) showed resistance and 14 strains (8%) intermediate susceptibility. Towards erythromycin, eight strains (4%) showed resistance and four strains (2%) intermediate susceptibility. Cross-resistance was demonstrated among the macrolides. Among the fluoroquinolones, intermediate susceptibility occurred with 42% of the isolates for sparfioxacin and 90% for ciprofloxacin; to the latter 5.1% proved resistant. The sum of intermediate and highly resistant isolates was 53% for chloramphenicol. Both penicillin-resistant strains were isolated during the last 2 years of collection and came from patients of non-Norwegian ethnic background. Imported strains appeared over represented among the strains resistant to penicillin and macrolides. Only imipenem and vancomycin showed full susceptibility for all pneumococci tested. An over representation of serogroup 6 strains was apparent among the strains with intermediate susceptibility and high resistance to benzylpenicillin. It is apparent that high-level resistance has, not so far, become a difficult problem in Norway. Nevertheless, the situation requires monitoring of the resistance level, particularly in meningitis and septic patients, and certainly in patients who cntail a higher than usual possibility of acquiring pneumococci from pools of resistant strains outside Norway (visitors, immigrants and recent returness from abroad).
Resistances to antimicrobials pose serious public health challenges. This issue concerns both human and veterinary medicine and can only be solved by a multidisciplinary approach. A comprehensive concept is, therefore, being worked out within the StAR (strategy antibiotic resistance) program in order to preserve the effectiveness of antibiotics for humans as well as animals. In this context, the AntibioticScout (www.AntibioticScout. ch) offers a new online tool for the prudent use of antibiotics in veterinary medicine. By involving all stakeholders, the guidelines included in the AntibioticScout will result in a nationwide accepted standard for the treatment of bacterial infections in animals. An additional system for the rapid reporting of cases of suspected lack of efficacy of antimicrobials is integrated to allow early detection of emerging resistance and the immediate launch of risk mitigation measures. A first version of the AntibioticScout for the treatment of dogs, cats and horses is available by the end of 2016. All stakeholders are now invited to contribute to the development of the AntibioticScout decision support.
Gram-positive bacterial pathogens are important causes of disease in cancer patients and are becoming increasingly resistant to available antimicrobial agents. We examined the in vitro activity of gatifloxacin, a new fluoroquinolone, compared with other quinolones, ceftazidime, and traditional Gram-positive-active agents tested against pathogens isolated from patients at 10 cancer treatment hospitals in the United States. A total of 1,128 Gram-positive isolates were tested by the E-test method (AB BIODISK, Solna, Sweden) with results validated by concurrent quality control strain analysis. Gatifloxacin was more potent than either ciprofloxacin or levofloxacin against all Gram-positive species. Vancomycin was the most active agent tested against all species except Bacillus spp., which were more susceptible to the fluoroquinolones. When tested against these Gram-positive pathogens from patients with cancer, the spectrum of gatifloxacin was also greater than that of levofloxacin and ciprofloxacin. Gatifloxacin may have a role as part of prophylactic or therapeutic antimicrobial regimens for selected cancer patients with Gram-positive infections.
Clonal changes of serotype 19A pneumococci have been appreciated in conjunction with growing prevalence of this serotype after implementation of the seven-valent pneumococcal conjugate vaccine (PCV7). In the present study, we characterized serotype 19A pneumococci collected in Russia within a decade preceding the implementation of PCV vaccination and described their clonal evolution. We retrospectively analyzed non-invasive serotype 19A isolates collected in 2002-2013. All isolates were subjected to multilocus sequence typing, antimicrobial susceptibility testing, determination of macrolide resistance genotype, molecular detection of pilus islet (PI) carriage, sequencing of penicillin-binding protein (PBP) genes. A total of 49 serotype 19A isolates represented 25 sequence types, of which 14 were newly described. The majority of isolates were distributed among clonal complex (CC) 663 (28%), CC230 (25%), CC156, and CC320 (14% each). CC663 and CC156 dominated in 2003, but were replaced by CC230 and CC320 later on; CC320 was only evident starting 2010. All isolates of CC663 and CC156 carried PI1; CC320 possessed both PI1 and PI2. The overall rate of altered amino acids in penicillin-nonsusceptible isolates was 13·9%, 7·2%, and 8·7% for PBP1a, PBP2b, and PBP2x, respectively. Our findings demonstrate that the clonal structure of serotype 19A pneumococci may evolve without PCV pressure.