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[Sensitivity of 858 strains of staphylococci to 27 antibiotics].

Susceptibility to 27 antimicrobial agents of 858 strains of staphylococci was determined. Tested strains belonged to the following species: S. epidermidis, S. saprophyticus, S. haemolyticus, S. hominis, S. simulans, S. warneri, S. cohnii, S. xylosus and S. intermedius. The antibiotics were: penicillin G, amoxycillin, augmentin, oxacillin, streptomycin, kanamycin, tobramycin, dibekacin, amikacin, gentamicin, sisomycin, netilmicin, doxycycline, minocycline, chloramphenicol, erythromycin, josamycin, clindamycin, pristinamycin, rifampin, fusidic acid, fosfomycin, trimethoprim, sulfamethoxazole, cotrimoxazole, and vancomycin. The ATB system was used, with the criteria for categorization recommended by the Antibiotic Sensitivity Testing Committee. Penicillin-resistance, that was found in all species, was high for hospital-acquired strains (67 to 75%) but also for some other strains (32% for S. simulans). Oxacillin-resistance varied across species (0% for the least prevalent hospital strains, 6% for S. epidermidis and 28% for S. haemolyticus). All strains were susceptible to vancomycin. For some drugs, resistance was a characteristic of the species: resistance to fosfomycin was often found for S. saprophyticus, S. haemolyticus, S. warneri, S. cohnii, and S. capitis; resistance to trimethoprim was common for S. simulans, and S. haemolyticus. S. haemolyticus was the most resistant species, a fact that justifies routine identification of this pathogen in clinical specimens.

Anti-Bacterial Agents↗

[Evaluation of the antibiotic sensitivity of Pseudomonas sp. using the API-ATB-PSE system. Comparison with diffusion and the reference agar dilution method].

In vitro activity of twelve antibiotics (ticarcillin, mezlocillin, azlocillin, piperacillin, cefoperazone, cefsulodin, ceftazidime, gentamicin, netilmicin, pefloxacin and ciprofloxacin) was determined by measuring minimum inhibitory concentrations (MICs) using agar dilution according to WHO recommendations, agar diffusion and the API-ATB-PSE system. One-hundred and forty-two Pseudomonas strains were studied. Five species of Pseudomonas were represented, i.e. aeruginosa, maltophilia, cepacia, stutzeri and paucimobilis. Isolates came from two Paris hospitals. Percentages of total agreement, minor discrepancies and major discrepancies between the results obtained with the API-ATB-PSE method and those recorded with the reference methods were determined. After checking the discordant strains, the results are discussed in order to evaluate the reliability of the ATB method for antibiotic susceptibility testing with Pseudomonas sp.

Agar↗

[The neuromuscular blocking activity of isepamicin sulfate (HAPA-B) compared with other aminoglycoside antibiotics].

Effects of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, on the neuromuscular transmission were studied in rats and compared with those of amikacin (AMK) or other aminoglycoside antibiotics. The HAPA-B, as well as other aminoglycoside antibiotics, depressed the twitch response of diaphragm to phrenic nerve stimulation in vitro. The depression effects of different drugs were compared and graded in the order of strengths of blocking action as: netilmicin (NTL) greater than gentamicin (GM) greater than streptomycin (SM) greater than kanamycin (KM) greater than AMK greater than HAPA-B. The IC50 (concentration which inhibited the response by 50%) of HAPA-B was 3.6 X 10(-3) g/ml. The neuromuscular blockade produced by HAPA-B was reversed by CaCl2, KCl or caffeine but not by neostigmine. D-Tubocurarine or MgCl2 augmented the neuromuscular effects of HAPA-B. Intramuscular (400 mg/kg) and intravenous (100 mg/kg) injections of HAPA-B did not affect the twitch response of gastrocnemius muscle to sciatic nerve stimulation in situ. Intravenous injection of 200 mg/kg caused death in some rats and depression of the twitch response in others. Intravenous AMK produced no significant effect on the twitch response at 50 mg/kg and caused death at 100 mg/kg. GM and SM caused death or significant degree of depression of the twitch response at intravenous doses of 50 mg/kg. In experiments of intravenous drug infusion for 60 minutes, the twitch response was depressed by HAPA-B at 400 mg/kg/hr and by AMK at 200 and 400 mg/kg/hr. In conclusion, HAPA-B has a neuromuscular blocking action presumably at the nerve terminal. However, its action was the weakest among the aminoglycoside antibiotics tested.

Amikacin↗

Aminoglycoside antibiotics: interaction with trimethaphan at the neuromuscular junctions.

Trimethaphan, a ganglionic blocking agent which is administered by intravenous drip to produce controlled hypotension during surgery, produces a complete neuromuscular blockade at the isolated phrenic nerve-hemidiaphragm preparation of the rat at a concentration of 0.3 mmol X l-1. This blockade is not reversed by neostigmine, a cholinesterase inhibitor, nor by calcium chloride, and this action is attributed to the local anaesthetic activity of the drug. Trimethaphan (1.5 X 10(-2) mmol X l-1) interacts with the following aminoglycoside antibiotics: gentamicin (0.04), streptomycin (0.05), netilmicin (0.06), amikacin (0.11), sisomicin (0.14), kanamycin (0.17), tobramycin (0.18) and dibekacin (0.21 mmol X l-1) to produce a complete neuromuscular blockade. These pharmacodynamic interactions of trimethaphan and aminoglycoside antibiotics occur at significantly reduced concentrations of the interacting drugs which are very close to the ones obtained after administration of therapeutic doses. When trimethaphan or aminoglycoside antibiotics are used alone at the above reduced concentrations they do not exert any neuromuscular blocking activity. The neuromuscular blockade which is obtained after the interaction of trimethaphan with aminoglycoside antibiotics is not reversed by either neostigmine or calcium chloride, although the neuromuscular blockade which is produced by aminoglycoside antibiotics alone is reversed by calcium chloride. It is concluded that the local anaesthetic effect of trimethaphan is the predominant factor of the mechanism of the above interactions. These interactions may produce severe respiratory disturbances (respiratory depression or apnoea) to the patients, during the perioperative period, which can be reversed only with artificial ventilation.

Aminoglycosides↗

[Antibacterial activities of arbekacin, a new aminoglycoside antibiotic, against methicillin-cephem-resistant Staphylococcus aureus].

The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows: Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains). Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED50's of GM, NTL and AMK were more than 2 mg/mouse. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.

Abscess↗

[Prevention of infectious endocarditis following manipulations of the urogenital tract].

Instrumentation of the genito-urinary tract may cause transient bacteremia, it can result in bacterial endocarditis in predispose subject. We studied the incidence of transient bacteremia following urogenital procedure and discovered a 2.6% rate in 196 patients. Therefore we studied antimicrobial prophylaxis against strains isolated from urocultures (35 strains) and blood cultures (6 strains). The strain's minimal inhibitory concentration (MIC) confirms antibioprophylaxis suggested by American Heart Association (AHA). Mean-while, according to our results, netilmicin is the best choice.

Adolescent↗

In vitro models in the study of antibiotic therapy of infections in neutropenic patients.

Most conventional methods for in vitro testing of antibiotics involve exposure of a bacterial inoculum to a constant, static concentration of drug. The in vivo concentrations of antibiotics change continually according to their pharmacokinetics. When two drugs are used, the ratios of their concentrations also change with time. The usual checkerboard tests for combined activity of two or more antibiotics do not consider the pharmacokinetic properties. An in vitro two-compartment pharmacokinetic model has been developed that presents changing concentrations of one or two antibiotics to isolated bacterial inocula. This model simulates the treatment of a bacterial infection in the absence of host defenses and thus mimics infection in a neutropenic patient. This model has been used to study the synergistic activity of beta-lactam/aminoglycoside combinations compared with conventional checkerboard and time-kill methods. Also, in this model, the addition of azlocillin or ceftazidime to netilmicin prevented the selection of resistant subpopulations of Pseudomonas aeruginosa that occurred with the aminoglycoside alone. In vitro pharmacokinetic models add kinetic parameters to conventional susceptibility testing and may prove useful in the design of trials of the optimal dosing and administration of antibiotics for infected neutropenic patients.

Agranulocytosis↗

Current state and tendencies of antibiotic resistance in Hungary.

This survey is based on data for 245 903 isolates reported by Public Health Network laboratories in 1983. Facultatively pathogenic Gram-negative bacteria comprised two-third of the isolates, and--except Escherichia coli--were resistant in a high percent to the most frequently used antibiotics. Oxacillin and vancomycin were the most effective against Staphylococcus aureus being in 94.7% resistant to penicillin. In contrast to other streptococci, all Streptococcus pyogenes strains were sensitive to penicillin. The majority of the Gram-positive strains were resistant to tetracycline. A comparison to results reported earlier (1974 to 1983) showed an increasing resistance rate mainly to ampicillin, carbenicillin, co-trimoxazole and gentamicin, which were introduced in therapy during this period. Resistance rate of almost all species has increased to gentamicin, e.g. that of Proteus mirabilis has risen tenfold. Emergence of Haemophilus influenzae resistant to ampicillin, and increasing resistance rates of P. mirabilis and Streptococcus pneumoniae to almost all drugs are remarkable findings. The increasing or variable usage of drugs that have been used for a long time did not influence resistance markedly. In some instances the resistance rates even diminished, e.g. the tetracycline resistance of agents associated with enteric diseases. A restricted use of chloramphenicol reflected in a decreased resistance of some species. Multiresistant Gram-negative strains--which are resistant to all drugs frequently used in Hungary--were isolated in 12.7% from a representative clinical material. The frequent occurrence of multiresistant P. mirabilis and Acinetobacter isolates is a new phenomenon. Surprisingly, the percentage of multiresistant E. coli strains was very low. Amikacin and netilmicin were found to be the most effective against multiresistant isolates.

Anti-Bacterial Agents↗

[Epidemiological study of a group of staphylococci isolated in a hospital environment].

A survey has been carried out on 336 strains of staphylococci isolated in a hospital environment in order to assess the validity of the lyogroup classifying method, to know their epidemiological behavior in our territory and to test their sensitivity to various antibiotics. The findings of the survey can be summed up as follows: the practical test for bacteriolysis activity appears to be a valid method of identifying staphylococci in so far as it allows to classify them, but also to differentiate them from micrococci; lyogroup VI appears to be prevalent both as a whole and in nearly all materials of origin; the incidence of resistance is highest for piperacillin (47%), gentamicin (20%), tobramycin (19%); it is lowest for netilmicin (1.2%) and amikacin (2.6%); among meticilline resistant strains (18%) there is a marked resistance towards nearly all antibiotics tested.

Anti-Bacterial Agents↗

[Bacteriostatic and bactericidal effect of cefotaxime combinations on Staphylococcus aureus assessed by FIC and FBC-index determination].

Activity of cefotaxime associated with one of nine other antibiotics (amikacin, dibekacin, gentamicin, netilmicin, sisomicin, tobramycin, erythromycin, clindamycin, and chloramphenicol) was studied by a checkerboard method with determination of FIC and FBC-indices. Four S. aureus strains were used: one homogeneous methicillin-resistant strain (S1), one heterogeneous methicillin-resistant strain (S2), and two susceptible strains (S3 and S4). Strong synergism between cefotaxime and aminoglycosides was found only for S2, with no significant differences between aminoglycosides (index # 0.3). Cefotaxime and chloramphenicol showed synergistic or additive bacteriostatic activities and consistently antagonist bactericidal activities. Bactericidal activities of cefotaxime and erythromycin were likewise antagonistic, whereas cefotaxime and clindamycin occasionally exhibited in vitro synergism.

Aminoglycosides↗

Pseudomembranous colitis and wound infection following perioperative use of multiple antibiotics.

The prophylactic use of antibiotics in elective surgery of the colon is accepted practice, but it has inherent risks. The authors report the case of a 70-year-old woman who had wound infection and severe, relapsing pseudomembranous colitis due to Clostridium difficile after a short course of antibiotics given orally and parenterally at the time of elective resection of the colon. Perioperatively, she received erythromycin base and neomycin orally, plus netilmicin and metronidazole intravenously. Although the concomitant administration of parenteral antibiotics may enhance the benefit of antibiotics given orally before operation, this does not entirely prevent wound infection. Until the relation between the number of drugs and risk of antibiotic-associated colitis is more clearly defined, caution should be exercised in the use of multiple antibiotics in elective colonic surgery.

Aged↗

Enzymatic modification of aminoglycoside antibiotics in gentamicin-resistant gram-negative bacteria.

An in vitro evaluation of 32 gentamicin-resistant, Gram-negative bacteria from hygiene-centres in Berne, Switzerland and Bratislava, Czechoslovakia, revealed that 24 strains produced gentamicin-modifying enzymes. Occurrence of acetyltransferases (AAC) was confirmed in 16 strains, adenylyltransferase (AAD) /2''/ was observed in 13 strains while 5 of the gentamicin-resistant strains produced both enzymes. All Czechoslovak strains were amikacin-susceptible, in amikacin-resistant Pseudomonas aeruginosa strains from Switzerland the presence of AAC/6'/ was found. In the majority of gentamicin-resistant, netilmicin-susceptible strains the occurrence of AAD/2''/ was observed. Gentamicin-resistance in the modifying enzymes producing strains was due either to production of an acetyltransferase or the adenylyltransferase except Swiss strains of Serratia marcescens where a simultaneous production of both types of the enzymes was noted. Twenty eight strains produced an enzyme modifying aminoglycosides of any kind.

Acetyltransferases↗

In vitro combination effects of cefsulodin, moxalactam and cefoperazone with four aminoglycosides on nonfermenting nosocomial gram-negative bacteria.

The activity of moxalactam, cefsulodin and cefoperazone on 67 non-fermenting gram-negative bacterial strains isolated from patients with nosocomial infections was tested either alone or in combination with gentamicin, tobramycin, amikacin and netilmicin, respectively, by use of the checkerboard agar dilution technique. Cefsulodin was most active against Pseudomonas aeruginosa, cefoperazone was the most active cephalosporin tested against Pseudomonas fluorescens-putida and Acinetobacter antitratus. Cefoperazone-aminoglycoside interactions were found to be synergistic in only 2--5% of all strains, cefsulodin and moxalactam in combination with aminoglycosides were most potent against P. aeruginosa. Cefsulodin-gentamicin interactions were superior to other cephalosporin-amino-glycoside combinations.

Aminoglycosides↗

Treatment of severe infections in patients with cancer. The role of new acyl-penicillins.

At the present time, gram-negative bacillary bacteremia in patients with neutropenia will respond favorably in 60% to 70% of the patients when carbenicillin-ticarcillin or cephalothin-cefazolin combined with aminoglycosides (gentamicin, tobramycin, sisomicin, netilmicin, or amikacin) are given. Piperacillin alone will cure 20/34 (59%) of bacteremic episodes in patients without granulocytopenia who have a severe underlying disease. In patients with neutropenia, the combination of piperacillin with amikacin was found to be associated with a favorable response in 76/121 patients (63%). These results are thus as good as those obtained with other broad-spectrum, beta-lactam antibiotics whether used alone in patients without granulocytopenia or in combination with aminoglycosides in patients with neutropenia. It seems likely that in patients with severe underlying disease and/or granulocytopenia, antibiotic combinations have reached an optimal efficacy. More attention should be paid to the correction of the basic predisposing factors to infection (granulocytopenia and immunodepression) and to infections caused by nonbacterial pathogens.

Amikacin↗

[Antibacterial effects of the combinations of azlocillin with other antibiotics].

Evaluating the synergistic effects of antibiotic associations is by no means an easy task owing to the diversity of the test methods utilized for this purpose. Data extracted from 11 reports published between 1975 and 1982 and concerning associations of azlocillin with various aminoglycosides (gentamicin, sisomycin, netilmicin, amikacin, tobramycin and dibekacin) and with two beta-lactam antibiotics (cloxacillin and cefotaxime) are reviewed in this article. On the whole, a synergistic effect against Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacteriaceae was most frequently observed with the azlocillin-aminoglycoside association. This effect was usually more pronounced with organisms showing low sensitivity to azlocillin and less pronounced with organisms resistant to aminoglycosides. As often pointed out, there is no general rule that would help predict with certainty from the sensitivity of a strain whether or not any given antibiotic association will act synergistically on that strain.

Aminoglycosides↗

[In vitro activity of combinations of cefotaxime and moxalactam with aminoglycosides on beta-lactamase-producing Enterobacteriaceae].

The in vitro synergistic activities of cefotaxime (Ctx) or moxalactam (Mox) in combination with gentamicin, amikacin, dibekacin or netilmicin were compared against 15 beta-lactamases non-producing or producing isolates of Enterobacteriaceae. The strains were classified according to their resistance to ampicillin (Am), carbenicillin (Cb) and cephalotin (Ce), but all were sensitive to the antibiotics tested in combination. In vitro checkerboard studies were performed using a microtiter technique for the selected strains. The FIC index was less than or equal to 0.62 for AmR CbR CeR strains (E. coli, E. cloacae, Serratia), for AmR CbS CeR strains (E. cloacae, Serratia, P. vulgaris) and for AmS CbS CeR strains (Serratia, P. morganii). These combinations were frequently additive (FIC = 0.75 - 1.0) against the AmS CbS CeS or AmR CbR CeS strains. Thus, the synergistic activities of Ctx and Mox in combination with an aminoglycoside seem to be correlated with beta-lactamase type produced by the Enterobacteriaceae.

Aminoglycosides↗

[In vitro study of combinations between third-generation cephalosporins and aminoglycosides on Enterobacteriaceae].

Four cephalosporins (cefotaxime, moxalactam, cefoperazone and ceftriaxone) were tested in combination with four aminoglycosides (gentamicin, tobramycin, netilmicin and amikacin). We examined 16 clinically isolates of Enterobacteriaceae of which 8 were resistant to newer cephalosporins. The synergy studies was evaluated with a microtiter checkerboard broth dilution. Studies of synergy revealed that cephalosporins in combination with amikacin were often synergistic against third generation cephalosporins resistant strains. These results suggest that amikacin may be facilitate the cephalosporin antibacterial activity.

Aminoglycosides↗

In vitro effect of some antibiotics on phagocytic index of human neutrophils.

The effect of the following antibiotics, in serum concentration equivalent to that of the usual therapeutic level, on the in vitro phagocytosis of killed Candida albicans by normal human neutrophils was studied: gentamicin, tobramycin, netilmicin, amikacin, aztreonam, cephradine, cefamandole, ticarcillin, spectinomycin, amoxycillin, clavulanic acid and Augmentin. Each antibiotic was tested 10 times. Results showed slight inhibition of phagocytosis by all antibiotics except amoxycillin.

Anti-Bacterial Agents↗