Search

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.

In this study we evaluated the in vitro activities of cefditoren--a broad-spectrum oral cephalosporin--and other comparator agents against 2,396 fresh isolates from community-acquired respiratory tract infections, collected from 6 clinical Italian microbiology laboratories. On penicillin-susceptible pneumococci and Streptococcus pyogenes, cefditoren demonstrated to be the most active antibiotic (MIC(90)values of 0.03 and 0.06 mg/L respectively), showing only a slight decrease in potency on penicillin-intermediate and resistant pneumococci (MIC(90)value 0.5 mg/L, 1.0 mg/L respectively). All the other comparators displayed MIC(90 )values of 4 - 8 mg/L for penicillins and of 4 to >64 mg/L for the oral cephalosporins. Cefditoren and levofloxacin were the most active against MSSA (MIC(90)0.5 mg/mL). Cefditoren displayed a uniformly potent inhibitory activity (MIC(90)of 0.03 mg/L) against all strains of Haemophilus influenzae, regardless of their ampicillin resistance (mediated or not by beta-lactamase production), while against Moraxella catarrhalis MIC(90)values were higher against beta-lactamase-positive (0.25 mg/L). Cefditoren was active also against Klebsiella pneumoniae and Escherichia coli : in this case its activity was comparable with that of levofloxacin. In conclusion, cefditoren, due to its potent activity, is a new effective therapeutic option for the treatment of respiratory tract infections.

Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent.

Background: Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms. The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae., Methods: Susceptibility tests were performed on 90, aerobic and anaerobic, bacterial strains, isolated from nasopharyngeal swabs and sputum. Minimum inhibitory concentrations (by microdilution) and minimum bactericidal concentrations were determined and compared., Results: Our selected panel of bacteria was highly susceptible to the antiseptics, particularly to chlorhexidine and naproxenate, even more so than two of the most frequently used antibiotics. Data were statistically significant (p < 0.005)., Conclusions: In view of their bactericidal and anti-inflammatory properties, these antiseptics may be effective in controlling the transitory colonization of the oral cavity by microbes that cause or worsen disease in patients with mild infections., (Copyright 2002 S. Karger AG, Basel)

We studied the in vitro susceptibility of 80 Helicobacter pylori clinical isolates to several antimicrobials commonly used to treat the infection, using the Epsilometer test (E-test). We also compared E-test and disk diffusion test in determining H. pylori susceptibility to the same antibiotics. We found a high prevalence of H. pylori strains resistant to metronidazole (23.7%), whereas the prevalence of H. pylori strains resistant to clarithromycin was 10%. Also, a significant correlation was found between MICs obtained with the disk diffusion test and E-test for metronidazole and clarithromycin. In conclusion, our study confirms a high prevalence of metronidazole- or clarithromycin-resistant H. pylori strains. Also, our data suggest that the E-test is a single, reliable, and cost-effective method to assess in vitro susceptibility of H. pylori to antimicrobial agents commonly used to eradicate the infection.

Aminoglycosides, widely used because of their large-spectrum antibiotic effects, should not interfere with the healing process of an ulcer or an infected wound. We evaluated the effects of amikacin or the excipients present in the topic formulation BG 90, powder 2. 5% (Boniscontro e Gazzone S.r.l., Rome, Italy), on human monocyte chemotaxis and the release of profibrotic factors by resting or lipopolysaccharide (LPS)-activated monocytes. The chemotactic response of monocytes to zymosan-activated serum is not modified in vitro by pre-incubation of the cells with amikacin (2 and 10 microg/ml/10(6) cells) or excipients. Unstimulated monocytes did not secrete appreciable amounts of cytokines. Vice versa, amikacin-stimulated cells released platelet-derived growth factor AB (PDGF-AB) (about 340 pg/ml), transforming growth factor (TGF)-beta1 (about 10 pg/ml), and tumour necrosis factor (TNF)-alpha (over 1,100 pg/ml); among excipients, ZnO and vitamin E induced PDGF-AB release (about 320 and, respectively, 200 pg/ml), while stimulation of monocyte monolayers by the other excipients did not lead to appreciable cytokine release. As expected, LPS-activated human monocytes produced PDGF-AB, TGF-beta1, and TNF-alpha. When monocytes were co-stimulated with LPS and amikacin, the PDGF-AB and TGF-beta1 values almost overlapped with those from the stimulation of cells with LPS alone, while TNF-alpha production was slowly reduced. The results show a stimulating effect of aminoglycoside on the production of profibrotic factors and, therefore, on the healing process of wounds in addition to a modulating effect on the production of pro-inflammatory cytokines like TNF-alpha. Moreover, ZnO and tocopherol (free-radical scavengers), used as excipients in the topic formulation, induce the release of growth factors with profibrotic activity (PDGF-AB). Further research is warranted to explore the effects of this formulation in vivo, verifying whether the association of the antibiotic with scavengers has a double advantage in topical amikacin: on the one hand, it could limit the damage from free radicals, and on the other it could favour tissue healing.

The 8-position side chain of 2-pyridones is believed to be involved in the binding with bacterial DNA gyrase to form the ternary complex, making them very important for the activity of 2-pyridones. A series of 2-pyridones having fluoro-substituted amines at the 8-position has been synthesized and their antibacterial activities and parmacokinetic properties are reported.

We compared the concentrations of dirithromycin and erythromycin at steady state in serum and the intrapulmonary region in patients suffering from acute exacerbation of mild chronic obstructive pulmonary disease. Twenty patients received dirithromycin, 500 mg given orally once daily for five consecutive days. The other 20 patients were treated with erythromycin base, which was administered orally four times daily at a total daily dose of 1000 mg for seven days. All patients were divided into eight groups, with five subjects in each group, according to sampling times (2, 4, 8, and hrs after the last dose) and treatment. After the erythromycin treatment mean serum concentrations were higher than those of dirithromycin treatment mean serum concentrations were higher than those of dirithromycin for upto 4 hours, but they were undetectable 24 hours after the last dose. At all time periods, the concentrations of dirithromycin in bronchial secretion, bronchial mucosa and epithelial lining fluid were greater than the concentration in serum. Concentrations of erythromycin were always lower than those of dirithromycin in the explored pulmonary sites. Our data demonstrated that a five day course of 500 mg of dirithromycin once daily induced higher concentrations and longer persistence in the various potential sites of pulmonary infection than a seven day course of 250 mg of erythromycin every 6 hrs. The shorter duration of therapy and the once daily dosing with good efficacy against common respiratory pathogens would be advantageous for patients and would be likely to promote better patient compliance and acceptability.

About 80% of nosocomial infections are caused by aerobic bacteria. The Pseudomonas aeruginosa is a Gram-negative bacterium pertaining to the Pseudomonadaceae family. P. aeruginosa is responsible for 6-22% of all hospital infections. The aim of this paper is to evaluate the efficacy of both hyperbaric oxygen-therapy (HBO 2 Atm x 35 min/day) alone for 8 days and when associated to the chemoantibiotic therapy (amikacine 15 mg/kg/day for 8 days intraperitoneal), in rats infected through pulmonary and subcutaneous intake. In rats affected by P. aeruginosa, HBO induces a significant reduction in mortality and morbility with bacteria eradication in blood culture findings, bronchial aspirate and skin biopsies. These effects were increased by the use of amikacine which is an antibiotic used for the treatment of Gram-negative bacteria.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Evaluation was carried out on the action of different antibiotics on the release of cytokines. Experiments were done in vitro on monocytes and on human lymphocytes. Results show that the majority of the antibiotics tested are able to induce the release of one or more cytokines from their respective producing cells. Among the beta-lactams the most active were the cephalosporins (cephalexin, cefamandol, ceftazidin, and a sulbactam-ampicillin combination) in inducing the release of TNF, IL-1 alpha, and IL-6 from monocytes, and releasing IL-4 and IFN-tau from lymphocytes. The sulbactam-ampicillin combination and cefamandole were extremely active in the production of IFN-tau. Among the lincosamides, clindamycine notably stimulated the release of TNF and IL-6, while lincomycine induced a notable increment of IL-4 from monocytes. Teicoplanin is a very strong inducer of TNF, IL-1 alpha and IL-6.