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PubMed1987

[Profiles of resistance to aminosides of Pseudomonas aeruginosa].

Among all Gram-negative bacilli, Pseudomonas aeruginosa is one of the most resistant to aminoglycosides. Five hundred and seventeen P. aeruginosa strains were studied. Isolates came from three Paris hospitals. Reference strains were provided by P. Courvalin and A. Philippon. The following aminoglycosides were used: streptomycin (S), spectinomycin (Sp), kanamycin (K), neomycin (N), gentamicin (G), sisomicin (Ss), netilmicin (Nt), tobramycin (T), amikacin (A), habekacin (H). The in vitro activity of antibiotics was evaluated by the standardized disk agar diffusion test. Distribution of inhibition zone diameters among susceptible strains were represented by histograms. Resistance frequency to aminoglycosides was: G: 61.5%, Ss: 38.1%, T: 35.8%, Nt: 58.2%, A: 15.5%, Seven resistance patterns were identified: G: 3%, G Ss: 3%, G Nt: 8%, G Ss Nt: 7%, G Ss T: 5%, G Ss T Nt: 53%, G Ss T Nt A: 21%. Hypothesis about resistance mechanisms and interpretation of disk agar diffusion test are discussed.

Aminoglycosides↗
PubMed1987

[Resistance of Listeria monocytogenes to cefotaxime and ceftriaxone combined with an aminoside].

The in vitro antibacterial activity of cefotaxime and ceftriaxone-aminoglycoside combinations was studied against 20 clinical isolates of Listeria monocytogenes, and compared with the activity of the antibiotics alone. Minimal bacteriostatic and bactericidal concentrations (MBCs) as well as killing curves were determined using different parameters. In all cases, the MBCs of gentamicin and netilmicin were shown to be lowered by addition of CTX or CTR. Using Mueller-Hinton broth the values of MBCs obtained were achievable in the CSF. However, the clinical bearing of these results remained to be discussed.

Aminoglycosides↗
PubMed1988

In vitro susceptibility of Listeria monocytogenes isolated from human blood and cerebrospinal fluid. A material from the years 1958-1985.

The in vitro susceptibility of 156 strains of Listeria monocytogenes isolated since 1958 from human cerebrospinal fluid or blood to twelve antibiotics was determined by an agar dilution technique. Erythromycin (0.05), trimethoprim (0.2), netilmicin (0.2), and penicillin (0.2) were the most active drugs on weight basis (MIC90 0.05-0.2 micrograms/ml). Ampicillin and imipenem had MICs for 90% of the strains of 0.4 micrograms/ml. Ceftazidime was inactive (MIC90 greater than 100 micrograms/ml). Comparison of susceptibility pattern between strains isolated in different years showed that the antimicrobial susceptibility of L. monocytogenes has not changed during the last 25 years. The minimal bactericidal concentration (MBC) of penicillin was determined by a macro tube dilution method in ten recent isolates. Penicillin was bactericidal for all the strains with a MBC of 0.4-3.1 micrograms/ml, i.e. one to three two-fold dilutions above the MIC of 0.2-0.8 micrograms/ml, which means that no tolerant strains were found.

Ampicillin Resistance↗
PubMed1988

Serotyping, sites of isolation and resistance of Pseudomonas aeruginosa.

407 strains of pseudomonas aeruginosa form in-patients and out-patients were serotyped according to Habs' schema. 11.3% of the isolates were non-typable and among the other strains serotypes 6 and 10 were the most prevalent (20.4 and 14.0%, respectively). Type 14 was not observed. Most of the strains isolated from sputum were non-typable, whereas serotype 6 predominated in specimens from urine, wounds and ears. The susceptibility of the isolates to antipseudomonal agents was estimated: 4.7% of the isolates (mainly serotypes 2, 4, and 11) were resistant to gentamicin and among these strains parallel resistance to tobramycin and netilmicin was observed in 47.4%.

Anti-Bacterial Agents↗
PubMed1988

[Serotype and susceptibilities to eight antibiotics of fifty strains of Pseudomonas aeruginosa isolated from clinical specimens and changes in susceptibilities of Pseudomonas aeruginosa to various antibiotics during a period between 1983 and 1986].

Efficacies of 8 antibiotics against Pseudomonas aeruginosa in the relation to serotypes and clinical sources were investigated on 50 strains isolated from patients at Nagoya Ekisaikai Hospital between August and September, 1986. Disk sensitivity test was carried out simultaneously for 5 antibiotics including piperacillin (PIPC), cefoperazone (CPZ), cefsulodin (CFS), ceftazidime (CAZ) and amikacin (AMK), using the single-disk method. We also examined changes in susceptibilities of P. aeruginosa to 5 antibiotics including PIPC, CFS, fosfomycin, gentamicin (GM) and AMK during last 4 years (1983-1986). The results are summarized as follows. 1. CAZ and AMK proved to have high antibacterial potencies, and their MIC80's (concentrations to inhibit growth of 80% of objective bacteria) were both 6.25 micrograms/ml. Following these two the order of potencies were; CFS, cefpiramide (CPM), PIPC, CPZ, netilmicin (NTL), and cefmenoxime (CMX). Sixty two percent of the strains of P. aeruginosa showed high resistances (MIC greater than 50 micrograms/ml) to CPM, CPZ, NTL and CFS, 58% to PIPC, and 2% to AMK. 2. With regard to serotypes, strains belonging to type E were less susceptible than those belonging to types G and I. Type E strains showed high resistance to all antibiotics except CAZ and AMK. 3. Strains obtained from pura and secreta were relatively susceptible, while those from urines were resistant, to these antibiotics tested, in general. 4. Good correlation between MIC's obtained with the agar dilution method (MIC less than or equal to 12.5 micrograms/ml) and these with the disk sensitivity test (greater than ¿ was observed. chi 2 statistical analysis showed that the results obtained with the 2 methods were closely related (P less than 0.01). 5. P. aeruginosa showed fairly high susceptibility to AMK through the recent 4 years (1983-1986). On the other hand, highly resistant strains against CFS, PIPC, FOM and GM increased rapidly during this period.

Anti-Bacterial Agents↗
PubMed1988

Comparative in vitro activity of imipenem against gram-positive and gram-negative aerobic bacteria from clinical isolates.

Imipenem is a member of a new class of beta-lactam antibiotics, carbapenems, with a very broad antibacterial spectrum. In this work we evaluated the in vitro activity of imipenem against a variety of bacterial strains isolated from clinical specimens as well as the activity of other beta-lactam antibiotics. The results obtained with 501 bacterial strains show that imipenem is active on both gram-negative and gram-positive microorganisms isolated from different infections. The in vitro inhibitory activity is greater than that of aztreonam, cefotaxime, ceftriaxone, piperacillin, amikacin, and netilmicin, against the majority of strains tested.

Anti-Bacterial Agents↗
PubMedDate not supplied

Amikacin-induced liver toxicity: correlations between biochemical indexes and ultrastructural features in an experimental model.

In previous studies, aminoglycosides (AG) as gentamicin (G), dibekacin (D), tobramycin (T), netilmicin (N) and Sysomicin (S) were proved to induce ultrastructural alterations in the liver of experimental animals. The aim of this studies is to investigate the effect of amikacin (AK) on rabbit liver which is commonly used in infections resistant to other AG; this was done studying both the common blood parameters and ultrastructural changes. The study was accomplished in 24 New-Zealand rabbits, twelve received 20 mg/kg AK every 12 hours for 2 weeks. Thereafter the animals were anesthesized and liver slices were obtained for transmission electron microscopy. As results obvious signs of primary and secondary microcholestasis associated to mitochondrial cristae detachment and phospholipid aggregations were noted; this last finding was less marked when compared to previous studies employing other AG. In the AK treated group, blood tests showed a significant increased in only Blood Urea Nitrogen (BUN) and an insignificant rise in AST levels. Our findings are consistent with an AK induced liver toxicity albeit less evident with respect to the other AG.

Amikacin↗
PubMed1979

Factors influencing the inactivation of aminoglycosides by beta-lactams.

Aminoglycosides and beta-lactam antibiotics were tested alone and in combination, via bioassay, in the presence of pH buffers at 6.5, 7.5 and 8.5; human serum; MgCl2 and CaCl2; clavulanic acid and beta-lactamase. Results show: inactivation of gentamicin, tobramycin, sisomicin and netilmicin is influenced by pH; clavulanic acid can inactivate gentamicin and tobramycin; and inactivation is influenced by salt concentration and constituents.

Aminoglycosides↗
PubMed1988

Bacampicillin, amoxycillin and talampicillin concentrations in bronchial secretions.

There are references in the literature describing the influence of bronchial inflammation on the antibiotic concentration in bronchial secretions, including netilmicin concentrations in the bronchial secretion of patients undergoing tracheotomy. Three semi-synthetic penicillins are compared--bacampicillin, amoxicillin and talampicillin--administered frequently in the treatment of various respiratory infections. The three antibiotics were administered successively for two days each, in the same patient, irrespective of other drugs. At the same time the cytologic evaluation of the degree of bronchial inflammation was done. The antibiotic concentrations in bronchial secretions and in sera were measured at the same time. The results showed that the concentration of antibiotics in bronchial secretions of patients undergoing tracheotomy was proportional to the degree of bronchial inflammation. Among the semi-synthetic penicillins investigated the highest degree of concentration in the bronchial secretion was obtained after the bacampicillin.

Amoxicillin↗
PubMed1988

The activity of antistaphylococcal drugs on nosocomial Staphylococcus epidermidis.

In reporting on the activity of cephalothin, cefamandole, FCE 22101, gentamicin, netilmicin, amikacin, rifampicin, clindamycin, josamycin, ofloxacin, ciprofloxacin, vancomycin and teicoplanin on 72 Staphylococcus epidermidis strains clinically isolated in the hospital, the Authors observed a high percentage of methicillin-resistance (68.05%) as well as resistance to other important drugs such as gentamicin (72.22%), rifampicin (27.7%), clindamycin (36.1%), and josamycin (40.27%). They also recorded good inhibitory activity of the studied beta-lactam drugs. However, this activity was not confirmed against methicillin-resistant strains when the test was performed under particular technical conditions (hypertonic medium, incubation at 30 degrees C, inoculum = 10(6)). The Authors also emphasize the poor bactericidal activity against these strains. The activity of quinolones was good; the activity of vancomycin and teicoplanin was very good on all strains studied.

Anti-Bacterial Agents↗
PubMed1988

Interaction of aminoglycoside antibiotics and calcium channel blockers at the neuromuscular junctions.

Aminoglycoside antibiotics (mmol.l-1) gentamicin (0.74), streptomycin (1.02), netilmicin (1.24), amikacin (2.23), sisomicin (2.74), dactimicin (2.75), kanamycin (3.43), kanendomycin (3.45), tobramycin (3.53) and dibekacin (4.35) produce a complete neuromuscular blockade at the isolated phrenic nerve-hemidiaphragm preparation of the rat, which is only reversed by calcium chloride. On the other hand, verapamil (2.04 mmol.l-1), a calcium channel blocker, also produces a complete neuromuscular blockade at the above preparation which is reversed by calcium chloride. Aminoglycoside antibiotics are potentially capable of interacting with verapamil and produce a complete neuromuscular blockade at concentrations significantly reduced. The neuromuscular blockade which is produced by the concurrent administration of the aminoglycoside antibiotics and verapamil is obtained with the usual therapeutic blood concentrations of the individual agents. Furthermore, the neuromuscular blockade which is produced during verapamil-aminoglycoside antibiotics interactions is completely reversed after calcium chloride administration. The mechanism by which aminoglycoside antibiotics and verapamil produce neuromuscular blockade must be the same. Both classes of drugs interfere with calcium ions movements through the calcium channels of the membrane of the motor nerve-endings inhibiting acetylcholine release at the synaptic cleft. The interaction of aminoglycoside antibiotics and calcium channel blockers is of clinical significance because when these agents are given concurrently during the perioperative period they may lead to respiratory depression or prolonged apnoea. These respiratory disturbances can be managed by slow intravenous infusion of 50 to 200 mg of calcium gluconate.

Aminoglycosides↗
PubMed1988

A study of the mechanism of action of aminoglycoside antibiotics on the guinea pig vas deferens.

Aminoglycoside antibiotics inhibit contractility of the isolated guinea pig vas deferens in a dose-related manner. However, total inhibition of the contractility cannot be attained, a phenomenon most probably attributed to the partial inhibition of the function of Ca channels by the antibiotics. The inhibitory potency of aminoglycoside antibiotics was found to be: sisomicin greater than gentamicin greater than netilmicin greater than streptomycin greater than dactimicin greater than amikacin greater than kanamycin greater than kanendomycin greater than dibekacin greater than tobramycin. Ca2+ antagonize the action of aminoglycoside antibiotics on the vas deferens competitively. This observation indicates that the untoward effect of aminoglycoside antibiotics on contractility of the vas deferens can be attributed to their ability to interfere with Ca2+ entry through cell membranes of the tissue, a prerequisite for subsequent contraction. Above a specific threshold (7.5 mM) Ca2+ have a prophylactic effect on vas deferens and prevent the inhibitory action of ICmax doses of the antibiotics. Thus, Ca could be used as a prophylactic medium or as an antidote in restoring contractility of the vas deferens if it is inhibited by aminoglycoside antibiotics.

Animals↗
PubMedDate not supplied

[In vitro evaluation of the antibiotic effect of imipenen on bacterial strains isolated mostly from compromised patients].

The antibacterial activity in vitro of Imipenem (N-formimidoyl-thienamycin) was studied on 237 recently-isolated nosocomial bacterial strains and compared with Aztreonam, Cefotaxime, Ceftazidime, Ceftriaxone, Piperacillin, Amikacin and Netilmicin through the determination of susceptibility by the Kirby-Bauer method. Taking into account that 65% bacterial strains, out of the examined ones, came from antibiotic high-pressure departments (45% from bone-marrow transplanted patients in the Hematological Department and 20% from Intensive Care Unit patients), the results obtained in vitro show an activity of Imipenem on Gram-negative bacteria as much as a 92.7% susceptibility and a 75.7% on Gram-positive bacteria; when compared with the activity of the other antibiotics, Imipenem shows a really excellent activity.

Drug Evaluation↗
PubMed1988

[Influence of aminoglycosides on the activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzymes].

Lysosomal enzyme activities can be modified by aminoglycosides. In this study, we have investigated the "in vitro" effect of gentamicin (G), tobramycin (T), dibekacin (D), netilmicin (N) and amikacin (AK) on urinary N-acétyl-beta-D-glucosaminidase (NAG) and its isoenzymatic forms. G, D and N are activators of this enzyme, specifically of the B isoenzymatic form, while T inhibits slightly the A, I1 and I2 forms. At usual therapeutical urinary concentration of AK during antibiotherapy, NAG and its isoenzymes are very strongly inhibited (more than 65%). Dixon plot indicates that the nature of inhibition is "competitive apparent", without binding of inhibitor to the active site of the enzyme. This binding of aminoglycosides to NAG as to other lysosomal enzymes may represent one of the accumulation mechanisms of aminoglycosides in tubular cells. It can explain the specific alteration of lysosomes during nephrotoxic antibiotherapy. Consequently, when urinary NAG determination is used as indicator of nephrotoxicity during therapy, the activation or inhibition of the enzyme by aminoglycosides could lead to false assay results.

Acetylglucosaminidase↗
PubMed1987

Imipenem/cilastatin versus aminoglycoside plus amoxicillin plus clindamycin in the treatment of serious postoperative infections.

In a prospective, controlled and randomized study, the clinical and bacteriological efficacy of imipenem/cilastatin was compared to that of a standard combination of an aminoglycoside (tobramycin or netilmicin), amoxicillin and clindamycin in patients with life-threatening postoperative infections. Doses used were imipenem/cilastatin 1 g q 8 h, amoxicillin 2 g q 8 h and clindamycin 0.6 g q 6 h. Aminoglycoside doses were individual and monitored six times weekly with serum concentration assays. Thirty-eight patients were entered into the study; 19 in each group. Diagnoses were pneumonia (five in the imipenem/cilastatin group and four in the combination group), peritonitis (eight in the imipenem/cilastatin and 13 in the combination group) and septicemia (five in the imipenem/cilastatin and two in the combination group). The two groups were comparable with respect to sex, age, underlying diseases and duration of antibiotic therapy. In the imipenem/cilastatin group, 14 patients were cured and one improved (79%). In the combination group, 11 were cured and 5 improved (74%). Four patients in the imipenem/cilastatin and five in the combination group failed to respond to treatment. In the former group 77% of the bacterial isolates were eradicated and 15% were suppressed. Corresponding frequencies in the combination group were 67% and 22%, respectively. Persistence of isolated pathogens was seen in 8% and 11%, respectively. It is concluded that imipenem/cilastatin seems to be an effective and well tolerated alternative to antibiotic combinations in the treatment of life-threatening postoperative infections. It also offers the advantages of fever antibiotic doses and renunciation of aminoglycoside serum concentration monitoring.

Adult↗
PubMed1987

In vitro activity of pefloxacin against gram-negative and gram-positive bacteria in comparison with other antibiotics.

The in vitro antibacterial activity of pefloxacin was evaluated against 310 gram-negative and 315 gram-positive aerobes, freshly isolated from clinical material. Reference antibiotics were: ofloxacin, ciprofloxacin, teicoplanin, vancomycin, rifampin, and methicillin for gram-positive cocci, and norfloxacin, nalidixic acid, ceftazidime, cefotaxime, piperacillin, netilmicin, gentamicin, amikacin, and aztreonam, for gram-negative bacilli. Gram-positive cocci were inhibited by 0.5 mg/l of teicoplanin, 1 mg/l of ciprofloxacin, 4 mg/l of both pefloxacin and ofloxacin, and 8 mg/l of vancomycin or rifampicin. Against gram-negative bacteria pefloxacin showed excellent activity, inhibiting 90% of all enterobacterial strains and 70% of other gram-negative aerobes at concentrations ranging between 0.03 and 4 mg/l. The same percentage of bacteria were inhibited by the other drugs at concentrations which resulted from two to fourfold higher than those of pefloxacin. MBCs and timed-kill tests indicated that this new agent is rapidly bactericidal against these isolates, and there were no significant differences in the rate of killing of both gram-positive and gram-negative bacteria. Inoculum size and pH did not change significantly the MIC values of pefloxacin.

Anti-Bacterial Agents↗
PubMed1986

Comparative in vitro studies on cefotaxime and desacetylcefotaxime.

After its parenteral administration in man, cefotaxime is partially metabolized to the desacetyl derivative (24-30% appearing in urine as desacetyl form). A detailed study was therefore carried out in vitro to compare the antibacterial activity against a wide range of clinical isolates and also the beta-lactamase stability of cefotaxime and desacetylcefotaxime, as well as other third-generation cephalosporins. The investigations of bacteriostatic and bactericidal activity were, in addition, extended to representative ureido-penicillins, cefuroxime, aminoglycosides and second-generation quinolones. Although cefotaxime was generally 4 to 8 times more active than its desacetyl derivative, smaller differences were observed against some strains of Enterobacteriaceae, Haemophilus influenzae and gonococci. A similar pattern was seen in relation to beta-lactamase stability, the parent antibiotic being generally more resistant to hydrolysis. Cefotaxime was, overall, the most active of the beta-lactam agents, except against pseudomonads, staphylococci and enterococci. In general, the antibiotic possessed comparable in-vitro efficacy to that of gentamicin, netilmicin and ciprofloxacin. Studies of combinations of cefotaxime and desacetylcefotaxime were carried out by the checkerboard method on solid media and also using a killing curve system in liquid media. A useful degree of synergy was observed against the majority of test organisms. This valuable effect could enhance the activity of cefotaxime in vivo, despite partial desacetylation.

Cefotaxime↗
PubMed1986

[Rapid ATB staph: 4-hour antibiotic sensitivity test of staphylococci. Description and performance].

Rapid ATB Staph is a method for four-hour antimicrobial susceptibility testing of staphylococci. The equipment and theoretical basis are identical to those already described for rapid testing of enterobacteriaceae. A standardized procedure is required to perform the test. The inoculum should be prepared from a culture no older than 24 hours and accurately standardized at 10(8). Temperature of incubation should be 35 degrees C to 37 degrees C; otherwise growth is delayed by approximately one hour. Time of incubation should not exceed 5 hours. Using these standardized conditions, rapid ATB Staph was compared with the reference agar dilution method for 22 antibiotics. Overall agreement was 96.3%. The rapid system is more sensitive than the reference method fort the detection of netilmicin and amikacin resistance; it is reliable for detecting penicillin resistance, oxacillin resistance and inducible resistance to erythromycin (agreement 96.7%, 94.8% and 98.4% respectively). A Rapid ATB Staph strip containing 15 antibiotics has been designed for routine susceptibility testing.

Anti-Bacterial Agents↗