netilmicin and Pneumonia

This article presents an overview of the aminoglycoside antibiotics used in clinical practice. Facts concerning the discovery and properties of the aminoglycosides are followed by information about spectrums of activity and mechanisms of action and resistance. Individual compounds are compared and proposals on the possibilities for their clinical use, both as single drugs and in combination with beta-lactam antibiotics, are made. The importance placed on measuring the serum concentrations of aminoglycoside antibiotics should serve as a remainder that this procedure is important, on one hand, to increase clinical efficacy and, on the other, to reduce the side effects of these antibiotics. Finally, the aminoglycosides are compared briefly with other antibacterial compounds, some of which are very new. There is no doubt that in the future the aminoglycosides will continue to occupy an important place in the treatment of severe infections, although newly developed agents appear to be effective complements.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Kanamycin; Kinetics; Neomycin; Netilmicin; Pneumonia; Sepsis; Sisomicin; Streptomycin; Tobramycin

To analyze clinical, bactericidal effectiveness and pharmacokinetics of wide-spectrum antibiotic netromycin (NM).. The trial entered 29 patients: 21 with bronchopulmonary diseases (pneumonia and chronic bronchitis), 5 with exacerbation of chronic pyelonephritis, 2 with infectious endocarditis and 1 with peritonsillar abscess.. Microbiologically, most of the agents (80.36%) showed sensitivity to NM. Pharmacologically, NM persisted long in blood serum and sputum irrespective of the administration mode. Positive clinical dynamics after NM treatment was achieved in all the patients but one who had a peritonsillar abscess.. NM is highly active against both gram-positive and gram-negative flora. Side effects are minimal.

Topics: Adult; Aged; Bacteria; Bronchitis; Endocarditis, Bacterial; Female; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Peritonsillar Abscess; Pneumonia; Pyelonephritis

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Topics: Adult; Aged; Bacteremia; Bacterial Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Netilmicin; Peritonitis; Pneumonia; Prospective Studies

Topics: Bacterial Infections; Clinical Trials as Topic; Diarrhea, Infantile; Female; Follow-Up Studies; Gentamicins; Humans; Infant, Newborn; Male; Netilmicin; Pneumonia; Sepsis; Urinary Tract Infections

Topics: Adult; Aged; Bronchitis; Clinical Trials as Topic; Double-Blind Method; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pneumonia; Respiratory Tract Infections; Sisomicin

The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.

Topics: Adult; Animals; Anti-Bacterial Agents; Cystic Fibrosis; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Endocarditis, Bacterial; Female; Gentamicins; Glomerular Filtration Rate; Guinea Pigs; Humans; Male; Netilmicin; Pneumonia; Pseudomonas Infections; Rabbits; Rats; Rats, Inbred Strains; Tobramycin

We describe the case of a 22 yr old male patient with cystic fibrosis, who, after long-term antibiotic treatment of pulmonary infection, developed a haemorrhagic diathesis with severe bleeding from the mucus membrane of the mouth, and haematuria. Rapid recovery was observed after infusion of vitamin K. During 8 months of follow-up, no evidence of recurrence of the clotting disturbances and anaemia were noted. The combination of impaired absorption of vitamin K due to underlying disease with the antibiotic-induced suppression of vitamin K synthesis by intestinal bacteria could be a possible explanation for this disorder.

Topics: Adult; Cefuroxime; Cephalosporins; Cystic Fibrosis; Follow-Up Studies; Gentamicins; Hemorrhagic Disorders; Humans; Male; Netilmicin; Pneumonia; Time Factors; Vitamin K

A major criticism of the use of aminoglycosides for the treatment of pneumonia is the poor penetration in infected airways. Once-daily dosing of aminoglycosides results in higher peak plasma concentrations without increasing toxic reactions and with optimization of pharmacodynamic properties. To predict intrapulmonary antimicrobial activity after once-daily dosing of aminoglycosides, it is necessary to determine the respective bronchial and alveolar disposition. We prospectively conducted a pharmacokinetic study of netilmicin following the first intravenous administration of a once-daily dosing schedule in 20 ventilated patients with pneumonia. A bronchoscopic sampling of bronchial secretions and a subsegmental bronchoalveolar lavage (BAL) were performed 60, 90, 120, and 180 min (five patients at each time point) on the first treatment day after intravenous administration over 30 min of 450 mg of netilmicin. The netilmicin concentrations in the alveolar lining fluid (ALF) were calculated using urea as an endogenous marker of dilution. In bronchial secretions, a peak concentration of 2.00 (SEM: 0.26) mg/L or 6 percent of the 30-min plasma concentration was reached at 120 min. In ALF, much higher levels were found. At 120 min, a peak ALF concentration of 14.7 (SEM: 2.22) mg/L or 41 percent of the 30-min plasma concentration was reached. Spearman's rank correlation testing failed to show a correlation between bronchial and ALF concentrations. Higher plasma concentrations of netilmicin after once-daily dosing give rise to ALF concentrations exceeding the minimum inhibitory concentration of susceptible respiratory pathogens involved in nosocomial pneumonia, while bronchial concentrations remain low. Aminoglycoside concentrations in bronchial secretions cannot be used to predict alveolar concentrations. Low diffusibility can no longer be considered as a disadvantage of aminoglycosides for treating pneumonias.

Topics: Adult; Aged; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Bronchoscopy; Drug Therapy, Combination; Half-Life; Humans; Lactams; Middle Aged; Netilmicin; Pneumonia; Respiratory System; Time Factors; Urea

Studies of therapy for experimental pneumonia due to Pseudomonas aeruginosa have failed to document beta-lactam-aminoglycoside synergy for most antibiotics examined, in contrast to results usually observed with pseudomonas infections at other sites. The neutropenic guinea-pig model of pseudomonas pneumonia was modified to resemble more closely therapy for clinical infections. Animals were treated 16 hr after infection with ticarcillin, azlocillin, ceftazidime, tobramycin, and netilmicin, alone and in combination. As predicted by in vitro synergy testing, in all cases combination drug therapy was more effective than the corresponding drugs given alone (P less than .05), as assessed by quantitative lung culture. Among single-drug regimens, those in which peak antibiotic levels did not exceed the minimal bactericidal concentration for the organism were significantly less effective. Resistance to aminoglycosides did not develop during therapy, and therefore, in this study does not explain the mechanism of synergy observed with beta-lactam antibiotics.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Azlocillin; Ceftazidime; Cephalosporins; Drug Synergism; Drug Therapy, Combination; Guinea Pigs; Netilmicin; Neutropenia; Penicillin Resistance; Penicillins; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin; Tobramycin

Topics: Adolescent; Adult; Bacteria; Child; Child, Preschool; Female; Gentamicins; Humans; Infant; Male; Microbial Sensitivity Tests; Netilmicin; Pneumonia

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.

Topics: Adolescent; Adult; Aged; Amputation, Surgical; Aorta, Abdominal; Aortic Aneurysm; Drug Evaluation; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Netilmicin; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Surgical Wound Infection; Urinary Tract Infections