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[A new method of antibiotic prophylaxis in liver surgery].

Ninety patients with focal affections of the liver were followed up. The patients were operated on the liver and treated therapeutically and prophylactically by means of the target-aimed release of antibiotics in erythrocyte ghosts. The antibiotics used were gentamicin and aztreonam. The results of the clinico-laboratory examinations showed that the target-aimed transport of the antibiotics in erythrocyte ghosts provided a 9-fold increase of the antibiotic level in bile and its 2-fold increase in the liver tissue. The time of the drug retention in the body fluids and tissues increased 2 times as compared to that provided by the routine treatment. The incidence of the postoperative purulent complications decreased 3 times. Such an effect is likely due not only to the target-aimed release of the drugs but also to the possible immunomodulating action of the prophylactic procedure used for preventing the complications that prevented as well the development of severe postoperative immune deficiency. Aztreonam proved to be more efficient in the prophylaxis of the postoperative complications.

Adult↗

[In vitro study of antibacterial activity of cefepime (Axepim) against gram negative bacteria: comparison with cephalosporins and other beta-lactams].

The susceptibility to cefepime and to other beta-lactams of 1017 inducible cephalosporinase-producing enterobacteria, 897 Pseudomonas aeruginosa strains, and 295 Acinetobacter baumanii strains was studied over a two-year period (July 1, 1993 to June 30, 1995). The isolates were from patients in visceral surgery, intensive care, and clinical hematology wards. Cefepime was compared to other third-generation cephalosporins and to imipenem, aztreonam, and the piperacillin-tazobactam combination. Cefepime was more active than the other cephalosporins against Enterobacter cloacae, Serratia marcescens and Citrobacter freundii. Activity of cefepime on the study isolates was also greater than that of aztreonam and of the piperacillin-tazobactam combination. Cefepime exhibited outstanding activity against Pseudomonas aeruginosa strains except those with the O12 serotype.

Acinetobacter↗

Sputum bacteriology and its antibiotic susceptibilities in Turkish cystic fibrosis patients.

To identify lower respiratory tract pathogens and their in-vitro antibiotic susceptibilities in Turkish cystic fibrosis (CF) patients, a total of 383 sputum cultures were evaluated from 45 CF children in 168 symptomatic and 215 control periods over 25 months. Microorganisms were isolated in 252 of the cultures. The isolation rate was 82 percent for symptomatic periods and 53 percent for control periods. The most common microorganism was P. aeruginosa in the symptomatic period and S. aureus in the control period. Other microbiological species included E. coli, H. influenzae, K. pneumoniae, S. epidermidis, beta-hemolytic streptococcus, H. parainfluenzae, K. oxytoca, E. aerogenes and E. aglomerans. P. cepacia was not found. In 20 cultures more than one microorganism was isolated at the same time. In in-vitro conditions, high susceptibility rates were detected to amikacin, ciprofloxacin and ceftazidim for P. aeruginosa; cefuroxime, ceftriaxone, amikacin, cephalothin, chloramphenicol and erythromycin for S. aureus; amikacin and ceftriaxone for E. coli; ampicillin-sulbactam, amoxicillin-clavulanate, cefuroxime, ceftazidime, ceftriaxone and aztreonam for H. influeanzae; and aztreonam and amikacin for K. pneumoniae. Lower respiratory tract pathogens and their antibiotic susceptibilities in Turkish CF children were not significantly different from those indicated previously in the literature.

Adolescent↗

[Antibiotic sensitivity of aerobic gram-negative bacilli isolated from severe infections in 1992: results of a French multicenter study. Groupe d'Etude d'Infections à bacilles à Gram Négatif (GEIGN)].

OBJECTIVES: Antibiotic susceptibility of 649 gram-negative bacilli involved in severe infections and isolated in 18 teaching hospitals from January to December 1992 was evaluated. METHODS: Minimal Inhibitory Concentrations were determined by agar dilution method for piperacillin, piperacillin+ tazobactam and imipenem, and by a microdilution method for 11 other antibiotics (amoxicillin, amoxicillin + clavulanic acid, cefotaxime, ceftazidime, aztreonam, ticarcillin, ciprofloxacin, fosfomycin, tobramycin, gentamicin, amikacin). Criteria of Comité Français de l'Antibiogramme de la Société Française de Microbiologie were followed for interpretation. Betalactamases were identified by isoelectric focusing and overproduction of cephalosporinase was defined by the resistance phenotype. The main species isolated were Escherichia coli (45%), Pseudomonas aeruginosa (14%), Klebsiella pneumoniae (7.8%), Salmonella spp. (7.5%), Enterobacter cloacae (4%) and Klebsiella oxytoca (4%). Most of the strains were isolated from blood culture (72.3%), respiratory tract (11.4%) and intraabdominal infections (8.6%). Most of the enterobacteria isolates were susceptible to imipenem, aztreonam, amikacin and ciprofloxacin (percentages of susceptibility were respectively 99.3, 98, 98.3 and 96.3); in most of cases clavulanic acid did not entirely restore sensitivity to amoxicillin of penicillinase-producing strains. Among 89 P. aeruginosa strains, 82% were susceptible to imipenem and ceftazidime, 81% to the association piperacillin + tazobactam and 51% to ticarcillin. Resistance rates are very high for Acinetobacter baumannii except for imipenem. CONCLUSION: Production of TEM-type penicillinase and over-production of the chromosomal cephalosporinase are the most widely observed mechanisms of resistance (respectively 22% and 9% of 649 strains). Prevalence of extended spectrum betalactamases was low (1%) and essentially observed for K. pneumoniae.

Anti-Bacterial Agents↗

[Clinical significance of the determination of ESBL (extended- spectrum beta-lactamase) production by gram-negative nosocomial bacteria].

BACKGROUND: Data on the incidence of multiresistant nosocomial bacterial strains of Xanthomonas (Stenotrophomonas) maltophilia, producing in addition to metallo-beta-lactamases also new types of broad spectrum beta-lactamases (ESBL) called for analyses of the production of different types of enzymes. METHODS AND RESULTS: Nosocomial multiresistant strains of Xanthomonas (Stenotrophomonas) maltophilia isolated from patients in 1996 were tested for the production of ESBL by a double diffusion disc test. The production of different types of ESBL was revealed, in particular production of ESBL specific for inactivation of aztreonam which is reversible by the action of clavulanate. The test of ESBL production, proved suitable also for orientation as regards selection of a suitable antibiotic in the treatment of infections caused by multiresistant or naturally resistant bacteria, possibly also the possible synergic action of antibiotics may be detected. The effect of mutual action of different antibiotics with a different inhibitory action of beta-lactamase inhibitors is illustrated when the test of ESBL production is used, where the effect of aztreonam on the inhibition of growth of ofloxacin resistant colonies was proved. CONCLUSIONS: The double diffusion test of production of new beta-lactamases (EBL) in multiresistant Gram-negative nosocomial strains made it possible to detect the possible synergic action of antibiotics in combination with the action of beta-lactamase inhibitors.

Cross Infection↗

[Resistance of Haemophilus sp. to antibiotics].

The present study was undertaken to determine the in vitro drug resistance of Haemophilus influenzae (68 isolates) and H. parainfluenzae (17 isolates). The tests susceptibility to Ampicillin, Amoxicilin/Clavulanic Acid, Cefaclor, Cefuroxime, Cotrimoxazole, Aztreonam, Ceftriaxone, Tetracycline, Ciprofloxacin, Rifampicin and Chloramphenicol were performed with a standard disk-diffusion method. The NCCLS methodology and susceptibility interpretative criteria were applied as described by the disk manufacturer. Beta-lactamase production was detected with nitrocefin impregnated disk (Cefinase, BBL Microbiology System). Resistance in nosocomially acquired Haemophilus isolates to several antibiotics was observed. Of the Haemophilus isolates 28.2% were Ampicillin in resistant, all were susceptible to the combination of Amoxicillin/Clavulanic acid. The Ampicillin-resistant strains were beta-lactamase producers. We observed the high resistance (70.1%) to Tetracycline and (28.2%) to SXT (Cotrimoxazole). All isolates of Haemophilus were susceptible to Ciprofloxacin. The low resistance percentages to Rifampin (1.2%), Aztreonam (3.5%) and Chloramphenicol (3.5%) was observed.

Drug Resistance, Microbial↗

[Sensitivity profiles of enterobacteria isolated at th Fann University Hospital Center, Dakar].

This study concerns 180 strains of Enterobacteria isolated at Fann University Teaching Hospital (Dakar, Senegal). The susceptibility to antibiotics was tested by disc diffusion test (antibiogram) and by dilution method determining the minimum inhibitory concentration (MIC). All of the species present more resistant profile to beta-lactams (> 55%); however ceftriaxon and aztreonam present the lower MIC 50 (< 0.06 microgram/ml). Fluoroquinolon inhibits more than 90% of the strains of E. Coli and Proteus. Chloramphenicol is active on Salmonella, but ceftriaxon, aztreonam and the fluoroquinolon present good alternatives. Cotrimoxazole is active only on 54% of Shigella strains.

Anti-Bacterial Agents↗

Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer.

BACKGROUND: Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. METHODS: A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. RESULTS: The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). CONCLUSIONS: This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed.

Administration, Oral↗

Intramolecular nucleophilic amino attack in a monobactam: synthesis and stability of (2S,3S)- 3-[(2R)-2-amino-2-phenylacetamido]-2-methyl-4-oxo-1- azetidinesulfo nic acid.

The potentially orally bioavailable arylglycine-substituted monobactam, (2S,3S)- 3-[(2R)-2-amino-2-phenylacetamido]-2-methyl-4-oxo-1- azetidinesulfonic acid, was prepared as a crystalline solid. No significant antibacterial activity [i.e., MICs were greater than 128 (micrograms/mL)] was found when the monobactam was tested against Gram positive and Gram negative bacteria. Solution instability (greater than 2,000 times less stable than aztreonam) due to intramolecular nucleophilic amine attack on the beta-lactam is believed to be a contributing factor to the poor microbiological activity.

Aztreonam↗

Colonization resistance of the human intestinal microflora: testing the hypothesis in normal volunteers.

Colonization resistance is the mechanism whereby the intestinal microflora protects itself against incursion by new and often harmful microorganisms. Some authors have claimed that colonization resistance is related to the integrity of the anaerobic flora, but this point has not been established in humans. In previous studies in our laboratory cefoxitin, piperacillin, cefoperazone or aztreonam were administered intravenously to healthy volunteers in order to study changes in the intestinal flora and acquisition of new strains. Seven of 16 antibiotic-treated subjects were colonized with gram-negative bacilli, but no correlation was observed between this colonization and the suppression of either anaerobes or any other component of the fecal flora. Marked strains of Escherichia coli and Pseudomonas aeruginosa were also administered by mouth in order to test acquisition of new bacteria. The fed bacteria were found in the stools of both antibiotic-treated and control subjects; the antibiotics had no apparent influence on the ability of these strains to colonize the intestinal tract. Our work, along with findings of others, supports the concept that colonization resistance occurs in humans and is diminished by antibiotic administration. However, it does not support the hypothesis that colonization resistance is related to the anaerobic microflora.

Anti-Bacterial Agents↗

In vivo significance of the inoculum effect of antibiotics on Escherichia coli.

The minimum dosage of antibiotics which reduced mortality in rats intraperitoneally inoculated with an Escherichia coli isolate was determined. Low mortality rates (0-10%) were obtained when antibiotics with minimal or no inoculum effect (cefoxitin, cefmetazole and gentamicin) were administered to yield serum levels 3 to 20 times the MIC, while antibiotics with a pronounced inoculum effect (cefotaxime and aztreonam) had to be administered to yield serum levels 200 to 1,000 times the MIC determined with a standard (low) inoculum. Thus, it seems that the inoculum effect observed in vitro with some antibiotics for Escherichia coli may have clinical significance.

Animals↗

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients.

The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric regimens in cancer patients) against recent bacterial isolates from patients with cancer. FK-037 was either equal to or 2 to 16-fold more active than the comparative agents against members of the Enterobacteriaceae. It was also active against Acinetobacter spp., Aeromonas spp., Pseudomonas aeruginosa, and other Pseudomonas spp. Xanthomonas maltophilia and Alcaligenes denitrificans were relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active against most gram-positive organisms (including some methicillin-resistant staphylococci) than was ceftazidime. Enterococcus spp., Listeria monocytogenes and Staphylococcus haemolyticus were relatively resistant to FK-037 and ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the majority of gram-positive and gram-negative isolates.

Aztreonam↗

In vitro activity of carumonam (RO 17-2301) and twelve other antimicrobials against clinical isolates of Pseudomonas aeruginosa.

Minimal inhibitory concentrations of the monobactam carumonam (RO 17-2301) and twelve other antimicrobials were determined using agar dilution against 140 recent non-replicate clinical isolates of Pseudomonas aeruginosa. The most active drugs were ciprofloxacin, amikacin, imipenem and ceftazidime, inhibiting 96, 91, 90 and 86 percent of the strains, respectively, at or below the susceptibility threshold. The monobactams carumonam and aztreonam were active against 78 and 65 percent of the strains, respectively. Tobramycin inhibited 68 percent of the strains, and gentamicin and netilmicin 50 and 21 percent, respectively. Analysis of correlation coefficients revealed a low correlation between imipenem and the other beta-lactams and a remarkably good correlation between the beta-lactams (excepting imipenem) and the aminoglycosides.

Aminoglycosides↗

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin.

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90% of Enterobacteriaceae isolates at < or = 0.25 microgram/ml, with the exception of Enterobacter aerogenes (MIC90 1 microgram/ml), Enterobacter cloacae and Citrobacter freundii (MIC90 8 micrograms/ml). In cefotaxime- and ceftazidime-resistant Klebsiella pneumoniae strains producing SHV-2 and SHV-6 beta-lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25-32 micrograms/ml). In Enterobacteriaceae strains hyper-producing chromosomally inducible beta-lactamases, FK-037 (MIC90 range, 0.25-8 micrograms/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime against Pseudomonas aeruginosa isolates, with MIC90 values of 16 micrograms/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressed Pseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12-2 micrograms/ml) and the other beta-lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 micrograms/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aztreonam↗

Balance of proinflammatory and antiinflammatory cytokines in mice immunized with Escherichia coli and correlation with mortality after lethal challenge.

The balance of proinflammatory and antiinflammatory cytokines, their correlation with endotoxin levels and mortality rate after lethal challenge of Escherichia coli was investigated in mice immunized weekly for 8 weeks with formalin-killed E. coli either untreated or treated with 0.5x minimal inhibitory concentration of aztreonam. Control mice treated in parallel with saline, died within 24 h after challenge with 100x lethal dose (LD50) of viable E. coli O6:K-. Mice immunized with antibiotic-treated bacteria showed a significantly higher survival than mice immunized with untreated E. coli. Cytokines were not detected in the sera of control mice during the entire period of immunization. At 90 min after immunization, mice immunized with antibiotic-treated E. coli showed tumor necrosis factor-alpha (TNF-alpha) levels significantly lower and interleukin (IL)-6 levels significantly higher (P < 0.05) than mice immunized with untreated E. coli, while comparable levels of interferon-gamma (IFN-gamma were measured in both groups. TNF-alpha and IL-10 levels measured 90 min after lethal challenge correlated with the mortality rate observed in each group (r = 0.96 for TNF-alpha and 0.94 for IL-10). IL-6 levels correlated with survival (r = 0.95), while IFN-gamma serum levels did not differ in the two immunized groups, but were significantly higher than those measured in the control mice. IL-4 was detected only after challenge of mice immunized with antibiotic-treated bacteria. Comparable levels of circulating endotoxin were measured after lethal challenge in both control and immunized mice. These data showed that in the presence of a protective immune response the survival of immunized mice was correlated with an early alteration of cytokine expression pattern including enhanced secretion of IL-4, IL-6 and IFN-gamma, and reduced secretion of TNF-alpha and IL-10.

Animals↗

Treatment of nosocomial postoperative pneumonia in cancer patients: a prospective randomized study.

BACKGROUND: Nosocomial pneumonia continues to be associated with high morbidity and mortality in cancer patients. METHODS: In an attempt to find an optimal treatment for this infection, nonneutropenic cancer patients with postoperative nosocomial pneumonia were randomized to receive either piperacillin/tazobactam (P/T) 4.5 g i.v. every 6 hours (30 patients) or clindamycin (Cl) 900 mg plus aztreonam (Az) 2 g i.v. every 8 hours (22 patients). Amikacin 500 mg i.v. every 12 hours was given to all patients for the first 48 hours. RESULTS: The two groups were comparable for the characteristics of pneumonia that included gram-negative etiology and duration of intubation. Response rates were 83% for patients who received P/T and 86% for those who received Cl/Az (P > .99). There were no serious adverse events; however, at our center the cost of the P/T regimen was $73.86 compared with $99.15 for the Cl/Az regimen. CONCLUSIONS: The two regimens had comparable high efficacy, and P/T had a slight cost advantage. Either of these antibiotic regimens combined with an aminoglycoside could lead to favorable outcome in cancer patients at high risk for nosocomial pneumonia.

Aged↗

Antimicrobial combinations in the therapy of infections due to gram-negative bacilli.

Antimicrobial combinations are used most frequently to provide broad-spectrum coverage; however, they are also frequently employed to enhance antimicrobial activity (synergism). Although there is extensive in vitro documentation of synergism for many antibiotic combinations, a clear advantage for these combinations has been difficult to demonstrate in clinical studies. Several types of combinations have been useful in clinical medicine and frequently result in synergism. These include combinations of a cell wall-active agent with an aminoglycosidic aminocyclitol, combinations of a beta-lactamase inhibitor with a beta-lactam, and combinations of agents that inhibit sequential steps in a metabolic pathway. Given its spectrum of activity, aztreonam will often be used with clindamycin or a beta-lactam antibiotic. Combinations of beta-lactams may be synergistic via several mechanisms. However, these combinations also exhibit significant potential for antagonism when used against gram-negative bacilli and, therefore, require careful evaluation prior to clinical use.

Aminoglycosides↗

Survey of antibiotic susceptibility among gram-negative bacilli at a cancer hospital.

A survey was conducted of the susceptibility of gram-negative bacilli to selected broad-spectrum antibiotics. The organisms were isolated from all patient specimens submitted to the routine microbiology laboratory during two three-month periods. Overall, the least resistance was observed against imipenem and ciprofloxacin. Considering all of the gram-negative bacilli, differences in susceptibilities to the other antibiotics (aztreonam, cefoperazone, ceftazidime, piperacillin) were minimal. Significant increases in resistance to some antibiotics occurred during the latter period.

Anti-Bacterial Agents↗