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PubMed1978

[Comparative studies on the nephrotoxicity of aminoglycoside antibiotics using renal enzyme elimination in rats as a model].

Determinations of renal enzyme excretion in rats inform on the relative nephrotoxicity of drugs. The data obtained in such studies are of clinical relevance. For the screening of new aminoglycosides, the renal enzyme excretion technique is a rather simple, but valuable model. New compounds can easily be compared to well-known ones about which clinical cata are available already.--Comparative investigations with netilmicin, a semi-synthetic sisomicin derivative, and with gentamicin are reported. Netilmicin in three different doses provoked significantly less increase in urinary alkaline phosphatase and "leucine aminopeptidase" activities.

Aminoglycosides↗
PubMed1982

[Comparative activity of cefsulodin on Pseudomonas aeruginosa, Acinetobacter and Enterobacteriaceae (author's transl)].

Cefsulodin, a new semi-synthetic cephalosporin, is characterized by its activity against P. aeruginosa. In this study the authors compared this new molecule with other four betalactamines, carbenicillin, ticarcillin, azlocillin and mezlocillin, and two aminoglycosides, amikacin and netilmicin. Two hundred and forty five strains studied were 100 Pseudomonas aeruginosa, 20 Acinetobacter, 42 Proteus, 21 Serratia, 22 Enterobacter, 20 Klebsiella and 20 E. coli. One hundred twenty strains of these showed carbenicillin resistant phenotype. MIC were determined by the agar dilution method. Cefsulodin was only active on Pseudomonas aeruginosa. MICs were at least 16 mg/l in the other species. On carbenicillin susceptible P. aeruginosa strains, the average MIC of cefsulodin, amikacin and netilmicin was 1 mg/l, and MICs of azlocillin, mezlocillin, ticarcillin and carbenicillin were 4-8 mg/l, 8 mg/l, 16 mg/l and 32 mg/l, respectively. On carbenicillin resistant P. aeruginosa, ticarcillin and mezlocillin were not effective and MICs of azlocillin and cefsulodin were 16 mg/l and 4-8 mg/l, respectively. However, MICs were between 64 and 128 mg/l in 20 p. cent of carbenicillin resistant strains.

Acinetobacter↗
PubMed1978

Comparison of neuromuscular effects and acute toxicity of some aminoglycoside antibiotics.

The correlation between acute toxicity and the effects occurring at neuromuscular junction level of some aminoglycoside antibiotics was investigated. Netilmicin (Sch 20569), sisomicin, gentamicin and kanamycin were administered i.v. in the rat and the following effects were studied: neuromuscular blocking activity (sciatic-gastrocnemius preparation), and acute toxicity evaluation. Neuromuscular blocking effects were found to be well correlated to acute toxicity data for all test-antibiotics. Comparison of results gave a sequence of relative potency which was as follows: netilmicin = sisomicin greater than gentamicin greater than kanamycin. Our findings confirmed that both respiratory failure, reporter as a side effect of the clinical use of aminoglycosides, and experimental toxicity follow the neuromuscular block.

Aminoglycosides↗
PubMed1995

[Single-dose therapy of infections of the lower urinary tract].

The authors analyze two clinical studies in the frame of single-dose treatment of uncomplicated infection of the lower urinary tract. The first study deals with comparison of the effect of netilmicin, ciprofloxacine and aztreonam. The second study deals with pefloxacine and cefuroxim-axetil. As the results implied, both long-term and short-term effectiveness of therapy comparable with other verified regimes was accomplished in female patients who were not pregnant and irrespective of their age. It is necessary to respect the contraindications of therapy. Chemotherapeutics which are appropriate for single-dose therapy of uncomplicated infections of the lower urinary duct include quinolones (pefloxacine, ciprofloxacine), phosphomycin-trometamol, co-trimoxozole a netilmicin. The majority of oral beta-lactam antibiotics cannot be recommended for a single-dose therapy of uroinfections. The authors summarize the advantages of a single-dose therapy of uroinfections and analyze the criteria of significant bacteriuria.

Adult↗
PubMed1994

[Resistance spectrum of staphylococci at the Vienna general hospital (July to December 1991)].

This study describes the antibiotic resistance of 1961 staphylococcal strains that were isolated at the University Hospital of Vienna from July to December 1991. Staphylococcus aureus (SA) represented 43.2%; coagulase-negative (CNS) staphylococci 56.8%, three quarters of which were Staphylococcus epidermidis. Excepting netilmicin, the proportion of resistant strains to all antibiotics was higher with CNS than SA. Methicillin resistance (M(r)) was found in 11.8% of SA and 30.3% of CNS. Borderline oxacillin resistance (BOR) was noted in 7.4% of SA and 32.5% of CNS. It is important to note that severe or generalized infections due to M(r) staphylococci should be treated with glycopeptide antibiotics such as vancomycin or teicoplanin from the very beginning, whereas chemotherapy of those with BOR strains may also be carried out with beta lactamase-stable beta lactam antibiotics. Comparing the results of this study with those of the first half of 1991, the respective proportion of M(r) staphylococci was significantly lower than 23.6% for SA and 47.6% for CNS recorded then. As compared with the foregoing period, however, these strains demonstrated increased resistance frequencies to gentamicin (from 81.3 to 90%), amikacin (from 35.4 to 69%), netilmicin (35.4 to 55%), and ciprofloxacin (56.2 to 64%). This is taken as an indication for the epidemic spread of a clone of resistant strains.

Anti-Bacterial Agents↗
PubMed1993

[Bacterial flora in laryngeal carcinoma and in postoperative scars of patients treated prophylactically by ciprofloxacin].

Microbiological investigations regarded samples from diseased tissue in patients with larynx carcinoma and in 53 patients. Samples were also taken two weeks after surgery from postoperative wounds. The patients received after surgery ciprofloxacin and metronidazole for five days. Cultures were incubated in aerobic and anaerobic conditions. Isolated microorganisms were tested by application of the API system susceptibility to ciprofloxacin, netilmicin and gentamycin were determined. Samples from cancerous tissue and postoperative wounds revealed most frequently presence of streptococci, staphylococci, Bacteroides and intestinal bacteria. It was found, however, that in investigated patients different bacterial flora was present when compared with previously tested cancerous tissue. Hemolytic streptococci and Staphylococcus aureus, and less frequently enterococci, were found much more frequently, Isolated strains were susceptible to ciprofloxacin (93%), netilmicin (76%) and gentamycin (39%).

Cicatrix↗
PubMed1993

[Daily single-dose aminoglycoside administration. Therapeutic and economic benefits].

Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity. Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Pharmacokinetic and microbiological data support this finding. Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing. The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Recommendations for once-daily dosing of netilmicin are given.

Aminoglycosides↗
PubMed1993

The treatment of Pseudomonas aeruginosa meningitis--old regime or newer drugs?

Currently intravenous ceftazidime with or without an aminoglycoside or alternatively ciprofloxacin are the recommended antibiotics of choice in Pseudomonas aeruginosa meningitis. A case of atraumatic, spontaneous Ps. aeruginosa meningitis in a child with acute lymphoblastic leukaemia is described. Despite the organism demonstrating in vitro sensitivity to ceftazidime, netilmicin and ciprofloxacin, intravenous therapy with these drugs failed to sterilise the cerebrospinal fluid (CSF). Both netilmicin and ciprofloxacin failed to attain therapeutic levels in the CSF. Intrathecal aminoglycoside therapy via an intraventricular reservoir was successful in eradicating the infection. In children with meningitis due to Ps. aeruginosa where intravenous therapy is unsuccessful despite in vitro sensitivity to recommended antibiotics; intraventricular medications should be commenced as soon as possible.

Anti-Bacterial Agents↗
PubMed1996

The evolution of aminoglycoside therapy: a single daily dose.

After five decades of clinical use, aminoglycosides continue to be important antibiotics in the management of gram-negative infections. However, antimicrobial therapy with gentamicin, tobramycin, amikacin and netilmicin has been complicated by the risk of nephrotoxicity and ototoxicity. Considerable research has been conducted to determine the optimal aminoglycoside dosing method that will produce maximum efficacy with minimal toxicity. Experimental data and clinical experience suggest that aminoglycoside regimens modified from standard dosing (every eight to 12 hours) to once-daily dosing may provide improved clinical outcomes, with reduced toxicity and cost of therapy. Gentamicin, tobramycin and netilmicin may be administered in single daily dosages ranging from 4 to 7 mg per kg, and amikacin may be given in a dosage of 15 to 20 mg per kg once daily.

Aminoglycosides↗
PubMed1995

[Synergic effect of a teicoplanin and cefpirome combination with aminoglucosides on enterococci. Therapeutic importance].

In this work we have evaluated the in vitro activity of teicoplanin and cefpirome to Enterococcus sp. combined with aminoglycosides gentamicin, tobramycin, netilmicin and amikacin. The combination with a greater percentage of synergy were teicoplanin plus tobramycin (70%), continued by teicoplanin plus gentamicin (69%) and teicoplanin plus netilmicin (58%). The combination of teicoplanin plus aminoglycosides results of great utility in the treatment os serious infections such as endocarditis, meningitis and bacteremia by enterococci, in allergic cases, or resistance to penicillin.

Aminoglycosides↗
PubMed1996

Aminoglycoside resistance mechanisms in Enterobacteriaceae and Pseudomonas spp. from two Danish hospitals: correlation with type of aminoglycoside used.

Sixty-two aminoglycoside-resistant Gram-negative enteric bacteria were isolated over a 3-year period from two hospitals (Bispebjerg and Esbjerg) among a total of almost 270,000 isolates. These hospitals were selected because of their different aminoglycoside policies during the years investigated. At Bispebjerg Hospital the principal aminoglycoside used was tobramycin, while gentamicin was the first choice at Esbjerg Hospital. Escherichia coli was the most frequently found aminoglycoside-resistant species. Among the 61 aminoglycoside-resistant strains studied, resistance was due to aminoglycoside-modifying enzymes in all except two Xanthomonas maltophilia strains. The ANT(2") enzyme occurred significantly more often at Esbjerg Hospital (p = 0.001), while enzymes of the AAC(3) or AAC(6') moieties were more common, but not significantly so, at Bispebjerg Hospital. The phenotypic pattern of aminoglycoside resistance, as determined by disc diffusion, correlated 100% with the ANT(2") and AAC(3)-V (the two most common enzymes among the isolates) genotype of the organisms as established using DNA probes. Median minimum inhibitory concentrations (MICs) (mg/l) for clinically utilized aminoglycosides were: amikacin (1.6), gentamicin (25.0), kanamycin (50.0), netilmicin (1.6-25.0) and tobramycin (12.5-50.0). Isolates from Bispebjerg Hospital revealed significantly higher MICs for netilmicin and tobramycin (p < 0.01) as compared to isolates from Esbjerg Hospital.

Aminoglycosides↗
PubMedDate not supplied

[Determination of serum aminoglycoside and vancomycin concentrations by the microbiological method in the presence of other antimicrobials].

The determination of serum concentrations of antimicrobials with a narrow therapeutic range by microbiological method requires some modifications when the patient is under combined antimicrobial therapy. The methodological conditions for the appraisal of aminoglycosides and vancomycin in the presence of other drugs were evaluated by using strains with selective sensitivity to the antimicrobial to be tested or by the adding crude extracts of beta-lactamases for the inactivation of the beta-lactam antimicrobials. These beta-lactamases were obtained from Enterobacter cloacae P99 (derepressed mutant) cultures for the inactivation of penicillins and first, second and third generation cephalosporins, as well as from Stenotrophomonas (Xanthomonas) maltophilia M 1484 cultures for the hydrolysis of imipenem. The strains allowing vancomycin appraisal and indifferent to the synergic activity of other drugs in the mixture were S. aureus M 2120, when the accompanying antimicrobials were gentamicin, ciprofloxacin or rifampicin, and E. faecalis M 2113, E. avium M 2091 and S. aureus M 2101 when the drugs in the mixture were amikacin, lincomycin or trimethoprim-sulfamethoxazole, respectively. For the appraisal of gentamicin in the presence of vancomycin or fluoroquinolones (ciprofloxacin or norfloxacin), E. coli M 1376 was the most suitable strain, while the use of K. pneumoniae ATCC 10031 was required for the appraisal of amikacin or netilmicin. When rifampicin was the accompanying antimicrobial, E. coli M 1495 turned out more adequate. E. coli M 1462 proved to be more satisfactory for gentamicin, amikacin and netilmicin dosages in samples also containing chloramphenicol, trimethoprim-sulfamethoxazole or tetracycline.

Aminoglycosides↗
PubMed1995

Renal function in premature infants during aminoglycoside therapy.

The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection-free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P < 0.05 and P < 0.01, respectively) and an increase in FENa and UCa/UCr in group C (P < 0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant.

Amikacin↗
PubMedDate not supplied

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with beta-lactams and aminoglycosides.

We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

Adolescent↗
PubMed1994

Antibiotic treatment of burned patients: an Italian multicentre study.

Antibiotic therapy in burn centres with highly specialized ICUs has reduced the mortality and morbidity in burn and trauma but, in spite of constantly improving supportive surgical and resuscitation methods, infection remains a major problem. Indeed, the clinical experience, as recorded in Europe and the USA, using different antimicrobial drugs and regimens, emphasizes a constantly evolving pattern of pathogenic microorganisms in the wound and in the rest of the patient's body, and their increasing chemoresistance. We report the preliminary results of 559 patients in a large controlled multicentre clinical study (mean age 41.4 +/- 17.8 years and burns covering a mean body surface area of 35.7%), with the collaboration of 13 of the 15 major Italian burn centres. The antibiotic treatment consisted of prophylactic administration of pefloxacin (800 mg i.v. OD for 4 days) for all patients as a first treatment while waiting for an antibiogram, and chemotherapy with teicoplanin (800 mg i.v. OD) together with netilmicin (300 mg i.m. OD) in one or more cycles. At random, half of the patients received thymostimulin (70 mg i.m. OD pro die for the first month and every other day thereafter until discharge from hospital). Of the bacterial pathogens involved in septic complications, 63.3% were Gram-positive (Staphylococcus spp. and Streptococcus spp.). The mortality rate was 15.5%. Pefloxacin chemoprophylaxis was successful in 19.4% of patients and cure or improvement was seen with combination chemotherapy in 66.7% of patients, mainly with only one treatment cycle. The incidence of mortality and sepsis was not significantly influenced by treatment with thymostimulin.

Adolescent↗
PubMed1988

Neonatal meningitis due to Gardnerella vaginalis.

A case of meningitis due to Gardnerella vaginalis occurred in a five-day-old newborn who had clinical signs of fever, polypnea and a grey complexion. After treatment with ampicillin, cefotaxime and netilmicin, the patient's condition improved, and no sequelae were observed. The bacterium isolated from a pure culture of the cerebrospinal fluid was identified by biochemical characteristics to be Gardnerella vaginalis, but it was not possible to define the source and mode of contamination.

Ampicillin↗
PubMed1987

In vitro susceptibility to aminoglycoside antibiotics in blood and urine isolates consecutively collected in twenty-nine European laboratories. European Study Group on Antibiotic Resistance.

The in vitro susceptibilities to gentamicin, tobramycin, amikacin and netilmicin were determined by a standardized microdilution method in unsupplemented Mueller-Hinton broth using blood and urine isolates from hospitalized patients in 29 laboratories in 12 European countries. The distribution of bacteria was similar in each laboratory, Escherichia coli and staphylococci predominating. While resistance rates varied between laboratories (e.g., rates of 1.1-34% were reported for gentamicin), they were consistently higher in southern Europe for all four antibiotics. Production of aminoglycoside-modifying enzymes was observed among resistant strains, ANT(2''), AAC(3)-V and AAC(6')-II predominating in gram-negative bacilli and APH(2)'' + AAC(6')-I in staphylococci.

Amikacin↗
PubMed1986

Comparison of the serum bactericidal activity of ceftriaxone/piperacillin and ceftriaxone/netilmicin.

The serum bactericidal activities of ceftriaxone, netilmicin, piperacillin and the combinations of ceftriaxone with each of the two other antibiotics were compared 1, 4 and 24 h after i.v. infusion in six volunteers. One hundred and one clinical isolates were used, including Staphylococcus aureus, Pseudomonas aeruginosa and various Enterobacteriaceae. The highest bactericidal titers were found against the Enterobacteriaceae, geometric means of 1:741 and 1:851 being obtained for ceftriaxone/netilmicin and ceftriaxone/piperacillin respectively. Against Staphylococcus aureus the geometric mean bactericidal titers of ceftriaxone/piperacillin (1:105) were markedly higher than ceftriaxone/netilmicin (1:35). Low bactericidal activity was exhibited by all drugs and combinations tested against Pseudomonas aeruginosa; a geometric mean bactericidal titer of 1:4.6 was achieved. The serum bactericidal activity of the double beta-lactam combinations was found to be at least equal to that of the combination containing a cephalosporin and an aminoglycoside.

Ceftriaxone↗