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PubMed1990

Comparative in vitro activity of several antimicrobial agents against selected clinical isolates.

A comparison between the in vitro activities of ceftazidime, cefotaxime, ceftriaxone, ampicillin, piperacillin, gentamicin, tobramycin and netilmicin was performed on selected clinical isolates. The activity of the agents was assessed by means of minimum inhibitory concentration determinations, and time-kill studies. The third generation cephalosporins were active against all members of the Enterobacteriaceae excluding some Enterobacter species. Their activity against these bacteria was generally comparable and greater than that of piperacillin. Netilmicin was the most active of the aminoglycosides tested against members of the Enterobacteriaceae; however, aminoglycoside-resistant strains were encountered. Ceftazidime was the most active of the third generation cephalosporins against the non-fermenters (e.g. Pseudomonas and Acinetobacter spp), its inhibitory activity also being greater than that of piperacillin. Using a time-kill study, ceftazidime also demonstrated greater bactericidal activity than piperacillin against an isolate of Pseudomonas aeruginosa. The aminoglycoside demonstrating the greatest activity against the non-fermenters was tobramycin.

Anti-Bacterial Agents↗
PubMed1990

Resistance to aminoglycosides: the situation in the Federal Republic of Germany.

The susceptibility of important pathogens to aminoglycosides was analysed using data from five studies encompassing different patient groups. Enterobacteria were generally sensitive to all modern aminoglycosides without marked differences. The frequency of resistance of Pseudomonas aeruginosa and other non-fermenters to gentamicin was 5-15% and to amikacin was 0-3%, and similar values applied for staphylococci. A higher rate of resistance was observed in pathogens isolated from urological patients: for non-fermenters resistance to gentamicin, tobramycin and netilmicin was 24-28%, whereas resistance to amikacin was 12%; and for staphylococci resistance was 33% for gentamicin, 48% for tobramycin and 9% for netilmicin. It is concluded that resistance to aminoglycosides is not an important problem in the Federal Republic of Germany, probably because aminoglycosides are used in combination with beta-lactam antibiotics, except in the case of urinary tract infections. Aminoglycosides are still important antibiotics, thus their rational use and constant surveillance are necessary to preserve their efficacy.

Acetyltransferases↗
PubMed1990

A prospective study of long-term use of amikacin in a paediatrics department. Indications, administration, side-effects, bacterial isolates and resistance.

Amikacin (Amikin; B-M) was used as the only aminoglycoside for 18 months in a paediatric department within a general hospital because of high levels of resistance of Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae isolates to tobramycin, gentamicin and netilmicin. Between 1 February 1987 and 31 July 1988, 816 children were treated with a slow intravenous injection at a standardised dose adjusted for weight and age. Respiratory disease was present in 35.8% of 537 neonates, 56.4% of 190 infants and 70.9% of 89 older children. Escherichia coli (65 isolates), Klebsiella species (59 isolates), Enterobacter species (26 isolates) and P. aeruginosa (22 isolates) constituted the most common Gram-negative pathogens. The positive blood culture yield was 7.8%. Satisfactory median peak and trough serum amikacin levels were achieved. No significant renal side-effects were noted. Severe bilateral hearing loss in 1 low-birthweight infant resulted from inadvertent overdosage. At the end of this 18-month surveillance period 97.7% of E. coli, 98.6% of K. pneumoniae, 96.3% of E. cloacae, and 98.0% of P. aeruginosa isolates remained sensitive to amikacin, while resistance of K. pneumoniae to tobramycin, netilmicin and gentamicin decreased significantly (P less than 0.003, P less than 0.001 and P less than 0.007 respectively; chi-square test).

Amikacin↗
PubMedDate not supplied

[Peritonitis in intermittent peritoneal dialysis: microbiological aspects and the antibiogram].

Peritonitis is the most frequent complication in patients on peritoneal dialysis and bacteria are the major causative agents. Initial antibiotic therapy may be "blind" but the antimicrobial agent used should be related to the infecting organism and its sensitivities. This study was initiated in order to evaluate the microbiological characteristics and sensitivity of bacteria isolated from pre and post peritoneal dialysis effluents. Positive growth of microorganisms was observed in 52 out of 503 cultures. Staphylococcus aureus and Staphylococcus epidermidis were identified most frequently (29 per cent each). Antibiograms showed high sensitivity to aminoglycosides (netilmicin and amikacin) and to second and third generation cephalosporin. Vancomycin and netilmicin were the best choices for Staphylococcal infection. A high bacterial resistance to ampicillin, co-trimoxazole, cephalothin and gentamicin was verified. Characteristics of organisms causing peritonitis in patients on intermittent peritoneal dialysis is very important, for selection of the initial antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1989

Biochemical determinants of aminoglycoside resistance in Gr- microorganisms isolated from urocultures.

The investigation was focused on 60 strains of Gr- microorganisms isolated from urocultures and resistant to gentamicin and/or amikacin. Resistance evaluation by the method of Bauer--Kirby with respect to 7 aminoglycoside aminocyclitols (streptomycin, spectinomycin, kanamycin, gentamicin, tobramycin, sisomicin, netilmicin and amikacin) as well as determination of minimal inhibitory concentrations revealed that the most frequently occurring resistance phenotype was streptomycin kanamycin gentamicin sisomicin tobramycin (91.66% tested microorganisms). Approximately 50% of all tested organisms were found to be susceptible to netilmicin. Assays for aminoglycoside-modifying enzymes using 32P ATP and 14C ATP confirmed APH(3')(5")--I and AAD(2") as resistance determinants regarding 4,6-substituted deoxystreptamines. Acetyltransferase determination by the method of Shannon and Phillips and that by van de Klundert et al. most frequently assumes for the formation of AAC(3)-II and AAC(3)-I. Assays utilizing radioactive labels in amikacin-resistant strains determine the enzymes APH(3') and AAD(2")-II.

Aminoglycosides↗
PubMed1986

[In vitro comparative study of piperacillin-aminoglycosides combinations against Enterococci and Enterobacteriaceae].

The hundred and ninety-two combinations were tested against 17 strains chosen from the results of MIC determination (disc method): 5 enterococci exhibiting low level resistance (r) or high level resistance (R) to streptomycin (S) and gentamicin (G): 2 strains Sr Gr, 2 strains SR Gr and 1 strain Sr GR; 12 enterobacteria chosen for their resistance phenotypes to beta-lactams and aminoglycosides and because they are the most frequent clinical isolates: 2 strains Amos Tics Ctns (group 1), 4 strains AmoR Tics CtnR (gr. II), 4 strains AmoR TicR Ctns (gr. III) and 2 strains AmoR TicR CtnR (gr. IV). MIC and MBC were assessed for the 17 strains (Mueller Hinton broth). Combinations were carried out by a checkerboard micromethod. FBC index was calculated for each combination. Against enterococci the 50 combinations were: piperacillin versus ampicillin + aminoglycosides (streptomycin, tobramycin, amikacin, gentamicin, netilmicin). Against enterobacteria piperacillin was combined with different aminoglycosides depending on their resistance phenotypes. These combinations were compared with ticarcillin or mezlocillin or cefotaxime + aminoglycosides (total number 142). The species studied produced different results: with the enterococci Gr synergistic effects (FBC = 0.62-0.75) were rare; additive and indifferent effects were predominant. With the GR strain some antagonistic effects were observed. With the enterobacteria, in groups I and II synergistic effects were frequent and almost equivalent regardless of the beta-lactam chosen. In groups III and IV (TicR) piperacillin MICs were greater than or equal to 128 mg/l and mezlocillin MICs greater than 512 mg/l; the synergistic effects were significant (FBC from 0.25 to 0.62). beta-lactam + amikacin or netilmicin, and especially piperacillin + amikacin, were found to have the most frequent synergistic effects upon the strains tested. Mezlocillin combinations cannot be used clinically; the use of piperacillin combinations requires further discussion. On the other hand, cefotaxime + aminoglycosides combinations are active against those TicR strains.

Aminoglycosides↗
PubMedDate not supplied

[Antibiotic resistance of Pseudomonas aeruginosa: a fact and a problem at the University Hospital Center of Cocody (Abidjan)].

The in vitro activity of 4 beta lactam compounds (carbenicillin, ampicillin, cefotaxim, azlocillin), 4 aminoglycosides (gentamicin, dibekacin, netilmicin, amikacin), chloramphénicol and tetracyclin chlorhydrate was studied on 30 strains of Pseudomonas aeruginosa. Amikacin is the most efficient with 97% of sensitive strains, then dibekacin (80%), azlocillin (76%) and carbenicillin (73%). Gentamicin and netilmicin are the less efficient with respectively 43% and 63% resistant strains. Chloramphenicol, ampicillin and cefotaxim have not any activity on these strains. This study reveals that 3% of the strains are polyresistant.

Anti-Bacterial Agents↗
PubMed1986

Susceptibility of enterococci. I. Inhibitory and bactericidal activity of several chemoantibiotics against Streptococcus faecalis and Streptococcus faecium.

The authors present a microbiological study of 100 strains of Enterococcus (70 strains of Streptococcus faecalis and 30 strains of Streptococcus faecium) tested for susceptibility to the following antibiotics, amoxicillin, ampicillin + flucloxacillin, piperacillin, rifampicin, vancomycin, netilmicin, ofloxacin, and norfloxacin. The assessment of minimum inhibitory and minimum bactericidal concentrations of these substances indicates that all have good inhibitory activity except netilmicin, which is active at higher concentrations; with rifampicin and vancomycin showing very poor bactericidal activity. The bactericidal activity of penicillins was hard to assess because of tolerance and paradoxical effect phenomena. The quinolones showed good inhibitory and bactericidal activity.

Anti-Bacterial Agents↗
PubMed1988

[In vitro antibacterial activity of cefpirome in combination with 4 aminoglycosides and 2 fluoroquinolones].

Combinations of cefpirome with aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) and of cefpirome with fluorinated quinolones (pefloxacin, ofloxacin) were tested against 20 Enterobacteriaceae, 6 Pseudomonas aeruginosa, 6 Acinetobacter calcoaceticus, 6 group D Streptococci and 6 Staphylococcus aureus strains, susceptible, intermediate or resistant with a low level to these different compounds. Activity of combinations was evaluated using a broth microdilution checkerboard method and FIC indices determination. Combinations of cefpirome with aminoglycosides demonstrated a synergistic effect in 79.5% of cases, but a strong synergy (FIC less than or equal to 0.62) was observed in only 46% of cases. The higher rate of strong synergy concerned Enterobacteriaceae (50% of cases) and group D Streptococci (58.3%). Combination of cefpirome with gentamicin was the most active against Enterobacteriaceae and with a lower degree against P. aeruginosa, A. calcoaceticus and S. aureus. Combination of cefpirome with netilmicin was the best association against group D Streptococci. Combinations of cefpirome with fluorinated quinolones demonstrated frequently and additive (40.9%) or indifferent (36.3%) effect. When a synergistic effect was proved, it was always weak (FIC = 0.75). Combinations of two fluorinated quinolones with cefpirome gave similar results. No combination was antagonist. This study is a primary estimation of activity of cefpirome combined with other agents. It will be necessary to confirm these results against strains resistant with high level, especially against cefpirome, strains not discovered in clinical isolates at present.

4-Quinolones↗
PubMed1988

Microbiological indications for the treatment of Staphylococcus aureus infections.

The Authors report microbiological data on the inhibitory activity of cephalothin, cefamandole, FCE 22101, gentamicin, netilmicin, amikacin, rifampicin, clindamycin, josamycin, ofloxacin, ciprofloxacin, vancomycin and teicoplanin against 165 clinically isolated Staphylococcus aureus strains. 34 of the study strains, i.e. 20.6%, were methicillin- and oxacillin-resistant. The activity of the tested drugs was good; the presence of nosocomial strains resistant to rifampicin (12.13%), clindamycin (13.94%), josamycin (18.2%), ofloxacin (4.85%), ciprofloxacin (12.7%), gentamicin (27.3%), amikacin (9.7%), netilmicin (7.9%) was noted. The Authors emphasize the good inhibitory activity of tested beta-lactam drugs against methicillin-sensitive Staphylococci, but also the limits of these drugs against methicillin-resistant strains. The activity of vancomycin and teicoplanin on all study strains was very good.

Anti-Bacterial Agents↗
PubMed1988

In vitro inactivation of aminoglycosides by cephalosporin antibiotics.

The in vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins complicates antibiotic assays. Due to the increasing number of new cephalosporins and use of aminoglycoside-cephalosporin combinations, we determined the in vitro stability of 28 aminoglycoside-cephalosporin combinations (gentamicin sulfate, tobramycin sulfate, netilmicin sulfate [10 micrograms/mL], and amikacin [20 micrograms/mL] in combination with cefazolin sodium, cefoxitin sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime acid pentahydrate, cefsulodin sodium, or cefpiramide sodium at 100, 200, and 300 micrograms/mL). These mixtures were incubated at 37 degrees C and sampled at 0, 8, and 24 hours. Amikacin and tobramycin were most stable and netilmicin was the least stable of the aminoglycosides. Cefoxitin, ceftazidime, and cefotaxime were the least inactivating of the cephalosporins. When combined with first- and second-generation cephalosporins, aminoglycosides are relatively stable, but some laboratory precautions may be necessary when determining aminoglycoside levels in the presence of third-generation cephalosporin compounds.

Aminoglycosides↗
PubMed1986

Drug-induced hemorrhagic cystitis.

A case of ticarcillin-induced hemorrhagic cystitis is presented, and the literature on drug-induced hemorrhagic cystitis is reviewed. A 12-year-old white boy with cystic fibrosis was hospitalized for an exacerbation of his pulmonary disease. Laboratory tests on admission showed an elevated white blood cell (WBC) count, 10-20 WBCs per high-power field (HPF) in urine, and normal BUN and serum creatinine. The patient was given ticarcillin i.v. (as the disodium salt) (final dosage of 320 mg/kg/day) in divided doses every six hours and netilmicin i.v. (as the sulfate salt) (final dosage of 4 mg/kg every eight hours). On day 7 the patient complained of painful urination, and urinalysis showed a 10-20 WBCs/HPF and 2-5 red blood cells (RBCs)/HPF. Two days later, the patient had gross hematuria, and urinalysis revealed 10-20 WBCs/HPF and 10-20 RBCs/HPF. Ticarcillin and netilmicin were discontinued and the patient's symptoms abated within 48 hours. Repeat urinalysis on day 11 showed no RBCs and 10-20 WBCs/HPF, with no casts or protein. Three months later, the patient was again hospitalized for an exacerbation of his cystic fibrosis. He was placed on tobramycin sulfate i.v. and ticarcillin i.v. (340 mg/kg/day). After the fourth dose of ticarcillin, the patient again complained of urinary pain and frequency and also reported gross hematuria. Urinalysis showed bacteria, 2-5 WBCs/HPF, and 5-10 RBCs/HPF; however, urine cultures were negative. Ticarcillin was discontinued and cefoxitin sodium i.v. was started. The patient's symptoms resolved within 36 hours, and a urinalysis on the fourth hospital day was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1986

Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses. A comparative biochemical and morphometric study.

The tissue repair subsequent to aminoglycoside-induced tubular necrosis has been evaluated for five different derivatives given at low doses. Gentamicin, dibekacin, netilmicin, and tobramycin were administered intraperitoneally three times a day at 10 mg/kg per day; amikacin was given intraperitoneally twice a day at 37.5 mg/kg per day. The drugs were administered for 4 or 10 days. Tissue regeneration in kidney cortex was assessed by: the rate of DNA synthesis (i.e., the specific radioactivity of DNA measured 1 hour after intraperitoneal injection of 200 microCi of [3H] thymidine per animal); the occurrence of less differentiated cells estimated by the morphometry of peroxisomes. In mature cells, identified by the presence of drug-induced myelin-like figures, peroxisomes occupied 3.0% of the cytoplasmic area, whereas in less differentiate cells devoid of myelin-like figures, the same organelles made 1.4% of the cytoplasmic area (mean values obtained from 20 treated animals). Gentamicin and amikacin were both shown to induce a dose-related enhancement of DNA synthesis in kidney cortex, except that the latter antibiotic was about 10 times less potent as compared to the former. When the five drugs were compared on the basis of their effect on DNA synthesis after 10 days of treatment, they gave the following ranking: gentamicin (5.6 times the mean control value) greater than or equal to dibekacin greater than netilmicin greater than tobramycin greater than amikacin (1.6 times the mean control value). The differences were less striking after 4 days of treatment. For each antibiotic, sections of proximal tubular cells obtained from four animals treated for 10 days (total surface, 2.10(4) microns2) were scanned for the presence of regenerative tissue (areas poor in peroxisomes). In gentamicin-treated rats, the areas poor in peroxisomes represented more than 18% of the scanned cytoplasmic surface in proximal tubular cells, as compared to about 4.5% in controls. The ranking of the five antibiotics according to the estimated area of undifferentiated tissue in proximal tubules was parallel to that found for DNA synthesis i.e., in gentamicin-treated rats undifferentiated tissue was much more prominent, as compared to amikacin-treated animals (about 6% of the scanned area). Since the relative extent of kidney cortex regeneration induced by each antibiotic at low dose is likely to reflect the degree of tubular necrosis, we conclude that the ranking outlined above indicates a difference in potential nephrotoxicity.

Aminoglycosides↗
PubMed1985

Aminoglycoside monitoring: timing of peak levels is critical.

Recommendations for optimal therapeutic peak concentrations of aminoglycosides are often not differentiated with respect to duration of infusion and timing of peak sample thereafter. To document the relevance of the timing, 139 dose intervals were analyzed in 58 patients during administration of gentamicin, amikacin, and netilmicin. Serum concentrations measured immediately after 30-min infusions were compared with concentrations obtained 90 min later (2 h values). The ratio of 30 min/2 h concentrations showed considerable variability. This ratio was less than 1.5 in 15% of the dose intervals analyzed and greater than 3 in 8% of the intervals. The poor correlation between concentrations measured at 30 min and at 2 h was documented by the coefficients of variation of 0.82, 0.30, and 0.67 for gentamicin, amikacin, and netilmicin, respectively. This variability was not explained by interindividual differences, renal function, or drug half-life. However, the initial decrease in concentrations was significantly lower in patients with impaired renal function (p less than 0.001). These data suggest that timing is critical for the sampling of serum to determine peak levels in patients and the definition of optimal therapeutic concentrations.

Aminoglycosides↗
PubMed1984

[In vitro study of the synergistic effect of cefmenoxime-aminoglycoside combinations apropos of 148 strains of Enterobacteriaceae].

The synergistic effect of cefmenoxime -aminoglycoside combinations against 148 Enterobacteriaceae strains selected for their resistance to beta-lactams was studied. Against the 89 Enterobacteriaceae with cefmenoxime MICs greater than or equal to 2 micrograms/ml, the rates of synergy were high : 73 % (netilmicin), 67 % (amikacin), 64 % (gentamicin) and 56 % (tobramycin). In contrast, cefmenoxime-susceptible strains (CMI less than 2 micrograms/ml) had lower rates : 47 % (gentamicin), 44 % (tobramycin), 43 % (netilmicin), and 42 % (amikacin). Synergistic effects on these bacteria are correlated to cefalotin resistance.

Aminoglycosides↗
PubMed1984

The effect of one prophylactic dosage of antibiotics on experimentally induced lethal intraabdominal sepsis.

In order to study the effect of one preoperative dosage of antibiotic on the mortality rate, incidence of abscesses, adhesions and intraperitoneal fluid, a previously described reproducible experimental model of intraabdominal infections in rats has been used. Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal microflora into a microflora similar to humans. The antibiotics tested were: doxycycline (1 mg), cefoxitin (40 mg), tinidazole (8 mg) + netilmicin (5 mg), clindamycin (150 mg) + netilmicin (5 mg) and trimethoprimsulfa (76.8 mg) + tinidazole (8 mg). The results indicate that one preoperative dosage of the antibiotic(s) significantly reduces the mortality rate in rats with intraabdominal sepsis. Intraperitoneal fluid was observed in all non-surviving rats, whereas in the surviving animals no fluid was present regardless of the type of antibiotic. The rate of intraabdominal abscesses was significantly higher in the doxycycline group compared with the other treated groups, indicating an inadequate anaerobic cover of doxycycline. The incidence of intraabdominal postoperative adhesions was similar in all groups except the trimethoprimsulfa + tinidazole group, which had a significantly lower number of rats with adhesions.

Abdomen↗
PubMed1984

Evaluation of automatic antimicrobial susceptibility testing with the MS-2 system.

We present the results of sensitivity of 191 Gram-negative bacteria towards the following antibiotics: aminoglycosides (amikacin, gentamicin, tobramycin, netilmicin), cephalosporines (moxalactam, cefotaxime, ceftazidime) and piperacilline obtained by agar diffusion method (Kirby-Bauer) versus automatic system MS 2 Abbott. Essential accord expressed in percentage is for amikacin 96%, for gentamicin 93%, for moxalactam 91%, for tobramycin 95%, for cefotaxime 92%, for piperacilline 89%, for netilmicin 90%, for ceftazidime 92. Full accord gives more discrepant results especially for cephalosporins. For aminoglycosides no significative differences were observed between the two methods. For cephalosporins the incidence of discordance was a little more high. A better sensitivity was obtained by Kirby-Bauer method versus automatic system, which can be considered a therapeutical tool as it furnishes rapidly (4 hours) MIC values, useful to establish antibiotic doses.

Aminoglycosides↗