Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A.

OBJECTIVE AND DESIGN: To evaluate the beneficial effects of exogenous NO and its levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two sequential insults. MATERIAL OR SUBJECTS: Eighty-six Wistar rats were submitted to different treatments and their tissue and blood samples were accessed at the end of the experiment. TREATMENT: Nitric Oxide was compared to Gentamicin as the tested guideline for our study. METHODS: Dacron graft implantation (first insult) and subsequent administration of Zymosan A((R)) (second insult) were performed in Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL: ); II) Laparotomy (L) + mineral oil (SHAM: ); III) L + Graft-Zymosan (GZ) (CONTROL: ); IV) L + GZ + Antibiotic (A) (ASSAY: I); V) L + GZ + NO (ASSAY: II) and VI) L + GZ + A + NO (ASSAY: III). Determinations: Survival, Bacterial Translocation, myeloperoxidase (MPO), Cytokines (TNF-alpha, IL-1beta, IFN-gamma), Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase, CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFkappaB. RESULTS: The model established induced a mortality rate of 20% and generated BT in all samples. It also significantly increased all variables, with P < 0.001 for MPO and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFkappaB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. NO, either alone or associated, reduced mortality to 0% and abolished BT, significantly decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines; P < 0.01 for OFR, and P < 0.05 for CAMs and for NFkappaB). CONCLUSIONS: The exogenous administration of NO before the two sequential insults prevented BT and controlled SIRS peripherally and at both cellular and transcriptional level in a lasting manner. In contrast, antibiotic treatment only exerted its action at peripheral level. The association of both treatments did not provide any important advantages.

In vitro activities of six new fluoroquinolones against Brucella melitensis.

We have tested the in vitro activities of eight fluoroquinolones against 160 Brucella melitensis strains. The most active was sitafloxacin (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 microg/ml). In decreasing order, the activities (MIC90s) of the rest of the tested fluoroquinolones were as follows: levofloxacin, 0.5 microg/ml; ciprofloxacin, trovafloxacin, and moxifloxacin, 1 microg/ml; and ofloxacin, grepafloxacin, and gatifloxacin, 2 microg/ml.

[Ampicillin-sulbactam activity against respiratory isolates of Haemophilus influenzae]. / Actividad de ampicilina-sulbactam frente a Haemophilus influenzae de origen respiratorio.

A study was conducted on the in vitro activity of ampicillin/sulbactam against 100 respiratory strains of Haemophilus influenzae (45 betalactamase positive and 55 betalactamase negative strains) simultaneously isolated during 1997 in 6 Spanish hospitals: Hospital Clínico San Carlos (Madrid), Hospital de Cruces de Basurto (Bilbao), Hospital La Fe (Valencia), Hospital Virgen Macarena (Seville), Hospital de Bellvitge (Barcelona) and Hospital Clínico Universitario (Salamanca). It was studied in comparison to amoxicillin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and ciprofloxacin. The MIC breakpoints used for the interpretation of data were those published by the National Committee for Clinical Laboratory Standards in 1997. All of the strains tested were susceptible to ampicillin/sulbactam, amoxicillin/clavulanic acid, cefuroxime and ciprofloxacin. The rate of resistance to clarithromycin was 55.5% for betalactamase positive strains and 38. 2% for betalactamase negative strains. A total of 23.6% of the betalactamase negative strains were resistant or showed intermediate susceptibility to amoxicillin but were susceptible to betalactam/betalactamase inhibitor combinations and cefuroxime.

In vitro activity of meropenem against ciprofloxacin-resistant enterobacteriaceae and Pseudomonas aeruginosa.

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (> 90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.

Multicenter Spanish study of ciprofloxacin susceptibility in gram-negative bacteria. The Spanish Study Group on Quinolone Resistance.

The susceptibility of 2,426 gram-negative bacteria obtained from 18 Spanish hospitals to ciprofloxacin was evaluated. Among different medical centers, susceptibility to ciprofloxacin ranged from 83 to 100% for Enterobacteriaceae, from 35 to 100% for Pseudomonas aeruginosa, from 0 to 100% for Xanthomonas maltophilia, Acinetobacter spp. and other gram-negative non-fermenting bacilli, and from 33 to 100% for Campylobacter spp. All clinical isolates of Haemophilus influenzae, Moraxella catarrhalis and Neisseria gonorrhoeae were susceptible to ciprofloxacin.

Susceptibilities of Brucella melitensis isolates to clinafloxacin and four other new fluoroquinolones.

The susceptibilities of 120 clinical isolates of Brucella melitensis and 3 reference strains of the same species to six fluoroquinolones (clinafloxacin, PD 117596, PD 131628, PD 138312, PD 140248, and ciprofloxacin) were examined by agar dilution MIC methodology. Clinafloxacin was the most active compound tested (MIC at which 50% of strains tested were inhibited [MIC50] and MIC90 of 0.06 micrograms/ml). Its level of activity was slightly higher than that of PD 117596 (MIC50 and MIC90 of 0.12 micrograms/ml). PD 131628 and ciprofloxacin were less active than clinafloxacin, with MIC50s ranging from 0.12 to 0.25 micrograms/ml and MIC90s of between 0.25 and 0.5 micrograms/ml for the two compounds. The activity levels of PD 138312 and PD 140248, with MIC50s ranging from 1 to 2 micrograms/ml and MIC90s of 4 to 8 micrograms/ml, were lower than those of the other fluoroquinolones tested.

In-vitro activity of four new fluoroquinolones.

The in-vitro activities of four new fluoroquinolones, E-4749, E-4874, E-4884 and E-4904, were compared with that of ciprofloxacin and sparfloxacin against 1106 clinical isolates. Against majority of Enterobacteriaceae, general antibacterial activities of E-4749 (MIC90s 0.06-1 mg/L), E-4874 (MIC90s, 0.03-0.25 mg/L) and E-4884 (MIC90s 0.01-0.5 mg/L) were comparable or slightly lower than those of ciproloxacin (MIC90s 0.01-0.25 mg/L) and sparfloxacin (MIC90s 0.01-1 mg/L). The activity of E-4904 (MIC90s 0.06-2 mg/L) was lower than those of its analogues. Most of the Escherichia coli which were resistant to ciprofloxacin (MIC > or = 2 mg/L) and Serratia spp., were resistant to the new fluoroquinolones. beta-Lactamase producing strains of Moraxella catarrhalis were very susceptible to these compounds (MICs < or = 0.008 mg/L). Most of Pseudomonas aeruginosa, non-aeruginosa Pseudomonas spp., Xanthomonas maltophilia, and Acinetobacter spp. were resistant to the new quinolones (MIC90s 8- > 16 mg/L). On the contrary, these new antimicrobials were active against the majority of the Aeromonas spp. (MIC90s < or = 0.5 mg/L). E-4749, E-4874, E-4884 and E-4904 remained active (MIC90s < or = 0.25 mg/L) against Staphylococcus aureus strains susceptible to methicillin. However, its activity was two- to eight-fold lower than that of ciprofloxacin (MIC90 0.03 mg/L) and sparfloxacin (MIC90 0.06 mg/L). Against S. aureus resistant to methicillin or ciprofloxacin, activity of these new compounds and comparators agents, was very low (MIC90s 2- > 16 mg/L). Most of the strains of Enterococcus faecalis were resistant (MIC90s > 16 mg/L). The activity of E-4874, E-4904 and sparfloxacin (MIC90 1 mg/L for each one) was higher than that of the rest of the agents tested. E-4874 (MIC90 0.25 mg/L) was four-fold more active than the other antibacterials tested (MIC90 2 mg/L) against Listeria monocytogenes. No new quinolone was active against Bacteroides fragilis (MIC90s 4-16 mg/L), Bacteroides thetaiotaomicron (MIC90s 8- > 16 mg/L), and other B. fragilis group (MIC90s 16- > 16 mg/L). Ciprofloxacin (MIC90s > 16 mg/L), and sparfloxacin (MIC90s 8-16 mg/L) also were inactive. E-4874 (MIC90 4 mg/L) was the most active quinolone tested against B.fragilis.

Activity of BAY y 3118, a novel 4-quinolone, against Brucella melitensis.

We have tested the in-vitro activities of BAY y 3118, a new chlorofluoroquinolone, ciprofloxacin, sparfloxacin, streptomycin, tetracycline and rifampin against 59 strains of Brucella melitensis. BAY y 3118 (MIC90 0.12 mg/L) was twice as active as sparfloxacin and tetracycline (MIC90 0.25 mg/L). The activity of ciprofloxacin, rifampin and streptomycin (MIC90 0.5, 2, and 8 mg/L, respectively) was, respectively, four-, sixteen-, and more than sixty-fold lower than that of BAY y 3118.

In vitro activities of new macrolides and rifapentine against Brucella spp.

We have tested the in vitro activities of streptomycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, erythromycin, four new macrolides (roxithromycin, azithromycin, clarithromycin, and dirithromycin), and rifapentine against 62 strains of Brucella spp. Azithromycin and clarithromycin were, respectively, eight- and twofold more active than erythromycins (MIC for 90% of strains = 2, 8, and 16 micrograms/ml, respectively). The activity of rifapentine was similar to that of rifampin (MIC for 90% of strains = 1 microgram/ml).