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PubMed1998

[Osmolarity of solutions used in nebulization].

Inhaled medications are widely used in patients suffering from bronchial diseases. Beside their pharmacological properties, nebulised solutions have physico-chemical characteristics that can alter bronchial reactivity. Non-isotonic solutions can induce a bronchial hyperresponsiveness and/or a severe bronchonconstriction. Nevertheless, multiple drugs are used for nebulisation despite their unknown osmolarity. The aim of this study was to measure the tonicity of drug solutions commonly used for nebulisation in patients suffering from bronchial disease. Drug solutions were prepared either according to manufacturer recommendations or by diluting the stock in 5 ml of NaCl (0.9%) or H2CO3 (0.14%). Although bronchodilatator solutions (i.e. salbutamol, terbulatine, ipratropium bromide) were nearly isotonic, some drugs prepared for nebulisation had either a very high (e.g. mesna, netilmicine) or a very low (e.g. gomenol, sodium cromoglycate) tonicity. These values may be responsible for bronchoconstriction. Some hypertonic solutions, prepared with drugs such as acetylcytein or netilmycin, are not commercialised for nebulisation but are commonly used for aerosol therapy. In addition, solutions initially isotonic could become significantly hypertonic towards the end of nebulisation. Taken together, these results suggest that non-isotonic solutions should be used with caution specially in patients with bronchial hyperresponsiveness, even when aerosol therapy is prescribed for upper airways.

Acetylcysteine↗
PubMed1988

Californium-252 plasma desorption mass spectrometry of aminoglycoside antibiotics.

This paper presents mass spectral data of eleven aminoglycoside antibiotics by using californium-252 plasma desorption (252Cf PD) mass spectrometry. This mass spectral data could be used to develop a confirmatory method for monitoring aminoglycoside antibiotic residues isolated from food products of animal origin. Mass spectra were determined by applying time-of-flight 252Cf PD mass spectrometry to eleven aminoglycoside antibiotics, namely: neomycin, kanamycin, paromomycin, tobramycin, apramycin, streptomycin, dihydrostreptomycin, amikacin, netilmicin, sisomicin and gentamicins. All eleven antibiotics yielded positive ion spectra. These hydrophilic antibiotics were derivitized to extractable chromopheric compounds. All but two antibiotics (streptomycin and dihydrostreptomycin) yielded nitrophenyl derivatives and spectra were obtained in both negative and positive ion modes. Derivatized aminoglycosides produced cation and anion spectra with quasimolecular ions corresponding to [M + H]+., M+, [M - H]-., [M + Na]+, [M + K]+ and M-. or [M - H]- and M-. or [M - H]-. Underivatized antibiotics were best examined in the positive ion mode. 252Cf PD mass spectrometry consistently produced very strong molecular or quasimolecular ions for all aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1998

Successful conservative treatment of nontyphoid salmonella endocarditis involving a bioprosthetic valve.

We report a first case of Salmonella enteritidis endocarditis involving a bioprosthetic aortic valve. Despite additional native tricuspid valve involvement, the clinical course was favorable using an antibiotic regimen of ciprofloxacin and netilmicin. Although Salmonella prosthetic valve endocarditis is considered an indication for surgical replacement of the prosthesis, this case indicates that prolonged treatment with fluoroquinolones may be an alternative provided that the hemodynamic situation is stable.

Aged↗
PubMed1984

In vitro inhibition of lysosomal phospholipases by aminoglycoside antibiotics: a comparative study.

Aminoglycosides induce an early and characteristic phospholipidosis in the lysosomes of kidney tubular cells. Inhibition of lysosomal phospholipase activity by gentamicin has been demonstrated in vivo and in vitro. Ten aminoglycosides have been examined for their potency in inhibiting phospholipases A1 and A2. Similar IC50's and IC90's (concentrations causing 50 and 90% inhibition) were found for sisomicin, dibekacin, gentamicin, tobramycin, kanamycin B and netilmicin. Kanamycin A, HABA-dibekacin and amikacin showed increasingly higher IC's. Thus, both the number and the position of amino groups are important. Streptomycin had little effect on phosphatidylcholine hydrolysis. Kinetic studies with gentamicin suggest a competitive type of inhibition. This approach may help for the in vitro screening of less toxic aminoglycosides.

Aminoglycosides↗
PubMed1996

Bacteria involved in the blockage of biliary stents and their susceptibility to antibacterial agents.

Endoscopically inserted stents are used for the palliation of obstructive jaundice, but infections and blockage of these stents by biliary sludge and bacterial biofilm may develop, presenting major complications. To analyze which bacteria are involved in this process, 25 biliary stents were examined. Eighty-one microorganisms were isolated: 59 gram-negative bacteria (54 Enterobacteriaceae and 5 Pseudomonas aeruginosa), 19 gram-positive bacteria (all Enterococcus spp.), and 3 Candida albicans. The Enterobacteriaceae were sensitive to netilmicin (100%), imipenem (98%), ciprofloxacin (96%), cefotaxime (69%), and piperacillin (57%), whereas Enterococcus spp. were sensitive to imipenem (79%), piperacillin (75%), ciprofloxacin (63%), and ampicillin (58%). The unpredictable aetiology and high rates of antibiotic resistance suggest that bacteriological monitoring is mandatory to avoid treatment failures in these patients.

Adult↗
PubMedDate not supplied

Animal studies on the reduction of aminoglycoside-induced nephrotoxicity by D-glucaro-1,5-lactam.

We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did not impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of beta-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.

Aminoglycosides↗
PubMed1979

The sensitivity of gentamicin-resistant gram-negative bacilli to cefotaxime, other cephalosporins and aminoglycosides.

The sensitivities of 80 gentamicin-resistant gram-negative bacilli to cefotaxime, cefuroxime, cefoxitin, cefamandole, cefazolin, tobramycin, netilmicin and amikacin were determined. Amikacin was the most active amino-glycoside. However, the percentage sensitivity to cefotaxime of most of the species was higher than, or equal to any of the other antibiotics tested. Cefotaxime was particulary active against Providencia spp., Serratia spp., Klebsiella spp., and Pseudomonas maltophilia, being 16 to 256 times more active than the next best cephalosporin or cephamycin. Clinical trials of cefotaxime are now required.

Acinetobacter↗
PubMedDate not supplied

Selection of antibiotics for treatment and prophylaxis of staphylococcal infections in cystic fibrosis patients.

Susceptibility in vitro of 179 staphylococcal strains from 107 cystic fibrosis patients against 31 antibiotics indicates that only teicoplanin, vancomycin and netilmicin were active against all strains. The use of betalactam antibiotics is impaired by 11.7% of methicillin-resistant strains. The bactericidal kinetics of cephalexin and flucloxacillin as determined in a pharmacodynamic model demonstrates the killing of strains resistant to cephalexin (MIC 8 mg/l to 32 mg/l) by flucloxacillin. For the rational selection of antistaphylococcal antibiotics for cystic fibrosis patients, both the MIC of the isolates and the concentration of the antibiotics in cystic fibrosis patients have to be considered.

Adolescent↗
PubMedDate not supplied

In vitro activity of combinations of antibiotics against Staphylococcus aureus resistant to gentamicin and methicillin.

Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.

Aminoglycosides↗
PubMedDate not supplied

The comparative activity of pefloxacin, enoxacin, ciprofloxacin and 13 other antimicrobial agents against enteropathogenic microorganisms.

In this study, we compared the activity of pefloxacin, enoxacin and ciprofloxacin against 269 enteropathogenic strains (Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella typhi, Shigella spp., Vibrio cholerae and Yersinia enterocolitica) with that of rosoxacin, flumequin, nifuroxazide, erythromycin, chloramphenicol, ampicillin, cefotaxime, tetracycline, amikacin, netilmicin, sulfamethoxazole, trimethoprim and co-trimoxazole. Pefloxacin, enoxacin and ciprofloxacin were always among the most active compounds. Furthermore, resistant strains or strains with elevated MIC values were not found. The MIC90 value for these three compounds was less than or equal to 0.25 mg/l, except for C. jejuni where it was 0.3 mg/l and 1.4 mg/l for pefloxacin and enoxacin, respectively.

Animals↗
PubMed1985

Cefotaxime in combination with other antibiotics for the treatment of severe methicillin-resistant staphylococcal infections.

Methicillin-resistant staphylococci (M-R staphylococci) represent 30% of the staphylococcal strains isolated in our hospital and pose important therapeutic problems. In a preliminary in vitro checkerboard study the bactericidal effect of various cephalosporins (cephalothin, cefamandole, cefotaxime and cefoperazone) in combination with other antibiotics (netilmicin, amikacin, vancomycin and fosfomycin) was studied on ten M-R staphylococcal strains. The combinations of cefoperazone with amikacin, cephalothin with vancomycin and of the four cephalosporins with fosfomycin were synergistic on the ten strains (FBC indexes less than or equal to 0.75). According to the CSF and bone levels achieved by these antibiotics and their bactericidal concentrations in combination, the combination of cefotaxime and fosfomycin was the most interesting, a concentration of less than or equal to 2 mg/l cefotaxime being bactericidal on five homogeneous M-R Staphylococcus aureus when combined with 4 mg/l of fosfomycin. This combination of cefotaxime (25 mg/kg, i.v. infusion over 30 min) and fosfomycin (50 mg/kg, i.v. infusion over three hours) three to four times daily was used to treat 16 patients: three patients with meningitis, six with bone and joint infections and seven with persistent bacteremia. The FBC indexes were less than or equal to 0.625 for the 12 strains studied. All the patients were cured without relapses. The concentrations of cefotaxime, desacetyl cefotaxime and fosfomycin in the CSF during meningitis three hours after the end of the infusion on the second day of treatment were 8.76, 6.82 and 58.0 mg/l, respectively, for patient one and 2.0, 0.53 and 31.0 mg/l, respectively, for patient two.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Impact of injectable cephalosporins on the gastrointestinal microflora: observations in healthy volunteers and hospitalized patients.

A disturbed microbiological ecosystem of the gut flora is frequently seen as a consequence of antibiotic therapy. Because this impact on the physiological balance is known to be causative for severe nosocomial infections and is mainly seen with antibiotics that are massively excreted via the bile (e.g. broadspectrum penicillins, ceftriaxone and cefoperazone), we investigated cefotaxime (CTX), cefotiam (CTM), cefmenoxime (CMX), ceftazidime (CAZ), ceftizoxime (CZX) and cefazolin + netilmicin (CEZ + NTL) in healthy volunteers. The respective daily i.v. doses, days of medication and numbers of volunteers were: CTX 3 g, 1 d, n = 8; CTM 6 g, 3 d, n = 15; CMX 4 g, 3 d, n = 15; CAZ 4 g, 1 d, n = 8; CZX 4 g, 1 d, n = 8; CEZ + NTL 2 X 3 g + 1 X 3 mg/kg/day, 4 d, n = 15. CTX was also investigated in 11 selected hospitalized patients. One or two stool specimens were taken before, during and several days after medication. The microorganisms were also tested for ampicillin and CEZ resistance on selective media. Ampicillin and CEZ resistance was much higher in hospitalized patients than in volunteers (mainly Proteus and Serratia sp.): 90% vs. 42% and 63.6% vs. 43%, respectively. CTX did not affect the anaerobes (Bacteroides sp. and lactobacilli) that are antagonistic to clostridia and Candida. No selection of strains resistant to ampicillin or CEZ occurred. In hospitalized patients, the level of resistance to these drugs was lower after treatment than before.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMedDate not supplied

Cefotaxime in urinary tract infections.

According to available studies the experience with cefotaxime in the treatment of urinary tract infections (UTI) is presented. Because of its broad spectrum antibacterial activity cefotaxime is active against most of the causative organisms, including multiresistant strains (except enterococci). Of 400 isolates cultured from 400 urological inpatients with complicated and/or hospital acquired UTI 90.2% of the gram-negatives and 87.7% of the staphylococci were inhibited by concentrations of less than or equal to 8 mg/l. As with other antibiotics in uncomplicated UTI, high cure rates could be achieved by single dose or short-term treatment. According to six non-comparative and nine comparative studies it could be demonstrated that treatment with cefotaxime achieved favorable results in patients with complicated and hospital acquired UTI even if caused by multiresistant strains. In general, in these studies cefotaxime was superior to gentamicin, cefoxitin, cefazolin and cefuroxime, but as effective as other third generation cephalosporins and aztreonam and as the combination of ampicillin and netilmicin. A good tolerance of cefotaxime was reported in all studies.

Cefotaxime↗
PubMedDate not supplied

Epidemiology of extended spectrum beta-lactamases.

Beta-lactamases play a major part in resistance, as recently redemonstrated by the emergence of extended spectrum beta-lactamases. Since its discovery in FR Germany, SHV-2 has been reported from four continents and CTX-1 (TEM-3) was established in at least 26 French hospitals. More than 12 other enzymes have been individualized. The newest aspect of resistance was probably underestimated because most strains of enterobacteria (mainly Klebsiella pneumoniae) appeared susceptible to oxyimino-beta-lactams as suggested by MICs or diameters of inhibition zone sizes. The double-disk synergy test between amoxicillin/clavulanic acid and oxyimino-beta-lactams was useful to easily detect two susceptibility patterns (CTX, CAZ). Extended spectrum beta-lactamases isolated among nosocomial isolates of enterobacteria (urines, blood, wound, sputum cultures) mostly from intensive care units have spread through hospitals. If outbreaks were described, numerous serotypes were identified in Klebsiella pneumoniae. In France the distribution of extended spectrum beta-lactamases showed that CTX-1 (TEM-3) was well distributed among ten species unlike SHV-type enzymes (SHV-2, SHV-3, SHV-4) preferentially detected in Klebsiella pneumoniae. A majority of strains produced CAZ-type enzymes in Escherichia coli. Some isolates produced two extended spectrum beta-lactamases. In Tunisia extended spectrum beta-lactamase producing strains were mainly identified among pediatric isolates of Klebsiella pneumoniae, Salmonella and Escherichia coli; SHV-2 was predominant but recently CTX-1 and two other types with an isoelectric point of 6.35 and 5.4 (phenotype CTX) were individualized. Because plasmid-encoded, this mechanism was spreading in France among enterobacteria with other resistance markers (e.g. netilmicin, amikacin) for CTX-1 unlike SHV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMedDate not supplied

Activity of 18 antimicrobial agents against multi-resistant strains of Staphylococcus aureus isolated from intensive care patients.

During an outbreak of infections with multiple-resistant Staphylococcus aureus, 22 strains were isolated from 12 patients between November 1983 and March 1984 on two surgical intensive care units at Kiel University Hospital. Susceptibility of all strains was tested with the disc diffusion method and a microdilution test using different inocula of 10(2) and 10(5) cfu/ml. All strains were resistant to beta-lactam antibiotics, including thienamycin as well as to gentamicin, clindamycin, doxycycline, erythromycin and fosfomycin. Rifampicin was the most active substance in terms of w/v, followed by fusidic acid, ciprofloxacin, vancomycin, and trimethoprim/sulfamethoxazole. Netilmicin and chloramphenicol showed only moderate activity in relation to the antibiotic breakpoint, but were considered sensitive according to the disc diffusion test. Caution should be reserved for the use of imipenem against multiply-resistant staphylococci.

Anti-Bacterial Agents↗
PubMed1996

Epidemiology of community-acquired Pseudomonas aeruginosa infections in children.

The epidemiology of community-acquired Pseudomonas aeruginosa infections in children during a one-year period (January through December 1993) was evaluated. A total of 6,859 clinical samples, each one representing a separate individual with suspected infection, were cultured. Pseudomonas aeruginosa was isolated from 218 children with various infections occurring in the following order of frequency: chronic suppurative otitis media, 76.3%; appendicitis/peritonitis, 10.3%; osteomyelitis, 8.9%; skin or soft tissue infection, 6.3%; acute conjunctivitis, 3.0%; and urinary tract infection, 0.1%. A variety of O serogroups were identified: O1 (15.2%), O6 (14.7%), O11 (12.4%), O10 (11.5%), O3 (10.6%), O5 (5.1%), and O9 (4.6%). Other serogroups and nontypable strains were recovered at a frequency of 11.2% and 14.7%, respectively. Nontypable strains predominated in chronic otitis media (18.9%), while serogroups O1 (18.3%), O6 (17.5%), and O11 (17.5%) were recovered most frequently among the typable isolates. Susceptibility of Pseudomonas aeruginosa to antipseudomonadal agents was extremely high. The rate of susceptibility to ceftazidime was 99.6%, to azlocillin 98.6%, to piperacillin 98.2%, to aztreonam 97.3%, to gentamicin and netilmicin 97.7%, and to ciprofloxacin 99.1%. All isolates were susceptible to tobramycin, imipenem, and amikacin. The results might suggest that community-acquired Pseudomonas aeruginosa infections in children can be treated successfully with any antipseudomonadal antibiotic.

Age Factors↗
PubMed1992

Susceptibility of frequent urinary pathogens to fosfomycin trometamol and eight other antibiotics: results of an Italian multicenter survey.

In order to assess the resistance profile for fosfomycin trometamol after several years of clinical use in Italy, this study has explored the susceptibility to fosfomycin and eight other antibacterial drugs of 6,021 strains isolated from 23,816 urines during 1990 in three teaching hospitals located in Genoa, Parma and Catania. Gram-negative strains, notably Escherichia coli (41.6%), were primarily involved. Amoxicillin was the least active compound with resistance in 41.4% of the isolates. Fosfomycin showed the lowest rate of resistance in both gram-negative (2.8%) and gram-positive (2.1%) pathogens. This was followed by norfloxacin with a resistance rate of 11.8% and netilmicin with 12.2%. These results indicate that fosfomycin-trometamol may continue to be used in single-dose treatment of urinary tract infections even in the absence of microbiological data since the prevalence of resistance to the drug is, at present, so low that therapeutic failure is highly improbable.

Anti-Bacterial Agents↗
PubMedDate not supplied

Incidence and mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa serotype O11 isolates.

Mechanisms of resistance to five aminoglycoside antibiotics: gentamicin (G), tobramycin (T), netilmicin (N), amikacin (A) and isepamicin (I), were assessed in 16 clinical isolates of Pseudomonas aeruginosa serotype O11, originating from five hospitals in Bratislava. All isolates were in vitro highly resistant to all mentioned aminoglycoside antibiotics (MIC > 32 mg/l). Thirteen isolates produced three aminoglycoside-modifying enzymes (AGME), responsible for resistance to the respective aminoglycosides: AAC(6')-I (T, N, A); APH (2") (G, T); APH (3')-VI (I). In addition to this, in four isolates a production of AAC(3)-II (G, T, N) was observed. In three isolates no production of AGME was observed. The strains studied were isolated mainly from urine. Several isolates were able to transfer aminoglycoside resistance by bacterial conjugation to P. aeruginosa 1008 rifr recipient. The transconjugants from these transfers expressed the same resistance pattern and nearly the same mechanisms of resistance as the donor strains.

Aminoglycosides↗