Antimicrobial agents

Forty-three Shigella sonnei isolates from adult patients with diarrhoea in Dakar were analysed for the presence of integrons. Isolates were resistant to sulphamethoxazole, trimethoprim, tetracycline, streptomycin and spectinomycin. A high prevalence of class 2 integrons (93%) was found. These integrons showed three distinct structures: a class 2 integron, part of the Tn7 family and its derivatives, carrying four cassettes in the order dfrA1-sat-aadA1-orfX; a truncated class 2 integron, without orfX; and a third type ca. 4 kb in size. These class 2 integrons probably play a role in the spread of multiresistance in S. sonnei isolates. To our knowledge, this is the first description of class 2 integrons in S. sonnei isolated in sub-Saharan Africa.

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.

ABSTRACTOne method that bacteria employ to reduce their susceptibility to antibiotics is the formation of biofilms. We developed a robust 6-well plate biofilm assay to evaluate early-stage discovery compounds against methicillin-resistantStaphylococcus aureus(MRSA). Tissue culture-treated 6-well plates were selected for this assay because they facilitate the adherence of MRSA and enable accurate determination of the number of CFU in each well. The MRSA biofilms formed in this assay exhibit increased tolerances to clinically used antibiotics. Using this biofilm assay, we identified a novel potentiator of gentamicin against MRSA biofilms. The combination of gentamicin and pentadecenyl tetrazole is superior to clinically used MRSA antibiotics against these MRSA biofilms. This novel combination also exhibits synergistic effects on MRSA planktonic cells. This plant-derived compound reveals promise for its effectiveness and warrants further lead optimization as an antibiotic and aminoglyc...

Ceftriaxone and ceftriaxone S-oxide behaved as inactivators against the metallo-beta-lactamase of Aeromonas hydrophila AE036 and as substrates for the zinc beta-lactamase produced by Bacillus cereus (569/H/9) and Stenotrophomonas maltophilia ULA 511. Moreover, RO 09-1428, a catechol-cephalosporin, was not recognized by the A. hydrophila enzyme. Panipenem, cephalosporin C, cephalosporin C-gamma-lactone, and loracarbef were substrates for the three studied beta-lactamases.

In view of the widespread emergence of resistant isolates, an attempt was made to isolate and characterise the component(s) of Ocimum sanctum with activity against Neisseria gonorrhoeae. Bioassay-guided purification of the hexane extract of leaves of O. sanctum was carried out, which yielded H12c as the active compound. H12c was characterised and was determined to be eugenol, with a minimum inhibitory concentration of 85–256 mg/L. The antigonorrhoeal efficacy of H12c was better against multiresistant strains. The 50% lethal dose (LD50) of H12c was found to be 2 g/kg body weight in rats. In view of its efficacy and lower toxicity, eugenol may be a potentially suitable molecule to be developed clinically in response to emerging resistant isolates of N. gonorrhoeae.

We evaluated the pharmacokinetics of amoxicillin-sulbactam (AMX-SUL), a novel drug combination, and its pharmacodynamics against Escherichia coli in 12 volunteers receiving a single oral dose (1, 000 mg). Peak serum bactericidal and urine inhibitory activities in most volunteers were observed against E. coli strains for which AMX-SUL MICs were low (2- to 4-mg/liter) (2 strains) and high (>/=16-mg/liter) (47 strains), respectively.

The goal of the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study was to determine antibiotic susceptibility to commonly used agents for urinary tract infections against outpatient urinary isolates obtained in various geographic regions in the USA and Canada. Forty-one medical centres (30 from the USA and 11 from Canada) participated, with each centre submitting up to 50 consecutive outpatient midstream urine isolates. Isolates were identified to species level by the standard protocol of each laboratory. Susceptibility testing was determined using the National Committee for Clinical Laboratory Standards (NCCLS) microdilution method. Resistance breakpoints used were those published by the NCCLS, including: ampicillin (resistant ≥32 μg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant ≥4 μg/mL), nitrofurantoin (resistant ≥128 μg/mL), ciprofloxacin (resistant ≥4 μg/mL) and levofloxacin (resistant ≥8 μg/mL). Of the 1990 isolates collected, 75.1% (1494) were collected from the USA and 24.9% (496) were collected from Canada. The mean age of the patients was 48.3 years (range 1 month to 99 years), and 79.5% and 20.5% of isolates were obtained from women and men, respectively. The most common organisms were Escherichia coli (57.5%), Klebsiella pneumoniae (12.4%), Enterococcus spp. (6.6%), Proteus mirabilis (5.4%), Pseudomonas aeruginosa (2.9%), Citrobacter spp. (2.7%), Staphylococcus aureus (2.2%), Enterobacter cloacae (1.9%), coagulase-negative staphylococci (1.3%), Staphylococcus saprophyticus (1.2%), Klebsiella spp. (1.2%), Enterobacter aerogenes (1.1%) and Streptococcus agalactiae (1.0%). Among all 1990 isolates, 45.9% were resistant to ampicillin, 20.4% to SMX/TMP, 14.3% to nitrofurantoin, 9.7% to ciprofloxacin and 8.1% to levofloxacin. Fluoroquinolone resistance was highest in patients ≥65 years of age. For the 1142 E. coli isolates, resistance rates were: ampicillin 37.7%, SMX/TMP 21.3%, ciprofloxacin 5.5%, levofloxacin 5.1% and nitrofurantoin 1.1%. For all 1990 isolates and for the 1142 E. coli only, resistance rates were significantly higher in US compared with Canadian medical centres. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates and demonstrates the continuing evolution of resistance to antimicrobial agents.

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephadrine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum und urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h-intervals. Bei äquivalenter oraler Dosierung hat Cefadroxil eine längere Serum-Halbwertszeit, eine langsamere Urin-Exkretionsrate und eine größere Fläche unter der Serum-Konzentrationszeitkurve als Cephalexin oder Cephradin und Serumspitzenkonzentrationen, die 75–80% derjenigen von Cephalexin betragen. Das errechnete Verteilungsvolumen in vivo von Cefadroxil ist größer als das von Cephalexin. Diese Eigenschaften führen zu einer längeren Verweildauer von Cefadroxil im Serum und Urin und zu einer längeren Exposition von Bakterien in vivo gegenüber Cefadroxil als gegenüber Cephalexin oder Cephradin. Weder Cefadroxil noch Cephalexin weisen bei wiederholter Anwendung eine Kumulation auf. Die mit Cefadroxil erzielten Serumspiegel werden von der Nahrungsaufnahme nicht beeinflußt. Die pharmakokinetischen Eigenschaften von Cefadroxil sprechen dafür, daß die Substanz eine klinische Wirksamkeit entfaltet, die die Gabe von Cefadroxil in zwölfstündlichen Intervallen zuließe.

Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80-90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd.