netilmicin and Sepsis

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

The aim of this study was to investigate the impact of parenteral nutrition on netilmicin pharmacokinetics in critically ill neonates during the first week of life.. A total of 200 neonates (gestational ages 26.4-41 weeks) treated with netilmicin (4-5 mg/kg in extended dosing intervals) for postnatal sepsis in the first week of life received either fluid therapy or parenteral nutrition. Netilmicin peak and trough serum concentrations were monitored and netilmicin pharmacokinetic parameters were compared with and without parenteral nutrition.. There were no statistically significant differences between the pharmacokinetic parameters of netilmicin (volume of distribution, elimination half-life, clearance) in critically ill neonates >32 weeks during the first week of life that received either fluid therapy or parenteral nutrition. For neonates <32 weeks this comparison was not feasible as the majority were parenterally fed.. Provision of parenteral nutrition (versus fluid therapy) in critically ill neonates >32 weeks did not significantly affect netilmicin pharmacokinetics and therefore does not require modification of recommended netilmicin dosage regimens.

Topics: Anti-Bacterial Agents; Critical Illness; Female; Food-Drug Interactions; Half-Life; Humans; Infant, Newborn; Male; Netilmicin; Parenteral Nutrition; Prospective Studies; Sepsis; Tissue Distribution

Since aminoglycoside efficacy is proportional to serum peak/MIC ratio and linked to post antibiotic effect, use of netilmicin once rather than twice a day has been proposed. On the other hand netilmicin might play a role in drug-induced nephrotoxicity, mainly on proximal tubule. Urinary retinol binding protein (RBP) and alpha1 microglobulin (alpha1m) are early and specific indicators of tubular damage and dysfunction. 21 preterm neonates (GA < 37 weeks) were divided in two groups on the basis of netilmicin administration modality (1: once a day, 2: twice a day, both for 7 days, at 5 mg/kg/die) and differences in netilmicin tolerability were assessed by evaluation of alpha1m and RBP levels by immunonephelometric method. No significant differences were found between the two groups either considering levels at time 1 and at time 2, or considering the difference between time 1 and 2 (Delta1/2). In our study once-daily dosing schedule shows similar low rates of nephrotoxicity, compared with multiple daily dosing schedule: this result may support the general adoption of once-daily dosing of netilmicin in clinical practice.

Topics: Alpha-Globulins; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Infant, Newborn; Infant, Premature; Kidney Tubules, Proximal; Male; Netilmicin; Retinol-Binding Proteins; Sepsis

The relationship between the volume of distribution, assessed according to the two-compartmental pharmacokinetic model, and extracellular water estimated by bioimpedance was studied in mechanically ventilated patients with sepsis and capillary leak. A prospective observational study was performed in a twenty-bed general intensive care unit in the university hospital. Patients received either vancomycin (n = 16) or netilmicin (n = 12) for more than 48 hours. Those with ascites, pleural effusion, on renal replacement therapy or with haemodynamic instability were excluded. Serum concentrations of drugs were taken for pharmacokinetic analysis before, 1 hour and 4 hours after the 30 minute infusion. Bioimpedance measurement was performed at the time of the third sampling. The protocol was repeated after 24 hours. Fluid balance during the 24 hour interval was recorded. Extracellular water was increased and represented 45.6 to 46.6% of total body water Fluid balance correlated with the change of extracellular water (r = 0.82, P < 0.0001) and total body water (r = 0.74, P < 0.0001). Volumes of distribution of vancomycin (0.677 +/- 0.339 l/kg) and netilmicin (0.505 +/- 0.172 l/kg) were increased compared to normal values. A correlation was demonstrated between volume of distribution (Vd(area)) of vancomycin and extra cellular water/total body ratio (r = 0.70, P < 0.0001). The central compartment distribution volume (V1) of netilmicin correlated with extracellular water/total body water ratio (r = 0.60, P < 0.003). Serum concentrations above the recommended therapeutic range were detected in 81.2% of patients on vancomycin and in 50% of patients on netilmicin. Increased volumes of distribution can be estimated by the bioimpedance measurements but are not associated with requirements for higher dosage of the glycopeptide or aminoglycoside antibiotics.

Topics: Anti-Bacterial Agents; Critical Care; Drug Monitoring; Humans; Metabolic Clearance Rate; Middle Aged; Netilmicin; Sepsis; Vancomycin

Aminoglycosides are frequently used to treat sepsis in patients with liver disease. However, it has been suggested that cirrhotic patients are particularly sensitive to aminoglycoside-induced renal dysfunction. We investigated the efficacy and incidence of renal impairment with netilmicin plus mezlocillin compared with ceftazidime in 128 cirrhotic patients who required empirical treatment for sepsis. Renal impairment developed in 8 of 63 (13%) patients receiving netilmicin compared with 2 of 65 (3%) patients receiving ceftazidime (P < .05); it occurred despite regular monitoring of trough netilmicin levels. Renal impairment was present at the time of death in 1 of 13 (8%) patients treated with ceftazidime compared with 5 of 9 (56%) of the netilmicin patients (P < .05). Mortality rates were similar in the two groups (ceftazidime 20%, aminoglycoside 14%; P = NS). Renal dysfunction is significantly more frequent in cirrhotic patients treated with netilmicin but with careful attention to dosage and fluid management the clinical effect is likely to be relatively modest.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Gentamicins; Humans; Kidney; Liver Cirrhosis; Male; Mezlocillin; Middle Aged; Netilmicin; Penicillins; Prospective Studies; Sepsis

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Burns; Child; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Interferon Inducers; Italy; Male; Middle Aged; Netilmicin; Pefloxacin; Sepsis; Survival Analysis; Teicoplanin; Thymus Extracts; Treatment Outcome

Twenty-eight patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were clinically studied for the effectiveness of the time-difference combination use of netilmicin (NTL) and minocycline (MINO). The patients were treated with NTL 100 mg and two hours later, with MINO 100 mg intravenously, twice daily, in the morning and evening for 14 days. Of 26 patients, MRSA was eradicated in 16 (61.5%), decreased in one, and unchanged in nine. Superinfections occurred with Serratia marcescens and Pseudomonas aeruginosa in two patients. The clinical efficacies were assessed in two patients with septicemia, 16 with pneumonia, and eight with chronic bronchitis. The obtained results were excellent in four patients, good in 15, fair in six, and poor in one patient. The rate of effectiveness was 73.1% (19/26). The overall clinical effectiveness judged by the committee was good in 19, fair in five, and poor in two patients. The efficacy rate was also 73.1% (19/26). Coagulase type II of MRSA was found in 23 patients, and coagulase type III in three patients, with overall clinical efficacy rates of 73.9% (17/23) and 66.7% (2/3), respectively. A side effect of eruption was observed in one patient, and its incidence was 3.6% (1/28). Abnormal laboratory test results were observed in 16 patients (57.1%), including abnormal liver function in 14 patients, abnormal kidney function in three, and increased eosinophils in three. Laboratory abnormalities occurred twelve of 16 bedridden patients, and this rate was higher than that in non bedridden patients. However, these abnormalities were all mild, transient, and immediately recovered after the treatment. In conclusion, the time-difference combination therapy using NTL and MINO was effective in the treatment of MRSA infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bronchitis; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Japan; Male; Methicillin Resistance; Middle Aged; Minocycline; Netilmicin; Pneumonia, Staphylococcal; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Superinfection

An open randomized study was done to compare the prophylactic value of single doses of netilmycin-metronidazole versus trimethoprim-sulfamethoxazole in the prevention of postoperative infections associated with transrectal prostatic biopsy. Of 117 patients enrolled in the study 101 were evaluated and of these patients 47 received netilmycin-metronidazole and 54 received trimethoprim-sulfamethoxazole. The bacteremia rate in the netilmycin-metronidazole group was 28% (13 of 47 patients) with a 95% confidence interval of 18 to 42% and in the trimethoprim-sulfamethoxazole group it was 37% (20 of 54) with a confidence interval of 26 to 50% (p = 0.43). None of the patients with bacteremia was symptomatic. Urinary tract infection rates were greater in the netilmycin-metronidazole group: 17% (8 of 47 patients) versus 2% (1 of 54) in the trimethoprim-sulfamethoxazole group, p = 0.01. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a better choice as an antimicrobial prophylaxis for patients undergoing transrectal prostatic biopsy.

Topics: Aged; Aged, 80 and over; Biopsy; Drug Combinations; Humans; Infection Control; Infections; Male; Metronidazole; Middle Aged; Netilmicin; Premedication; Prostate; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Twenty one patients with serious Staphylococcus aureus infection and bacteraemia were randomized prospectively to receive either teicoplanin and netilmicin or flucloxacillin and netilmicin. After at least 48 h of treatment serum samples were collected for the determination of trough and peak antibiotic concentrations, the serum killing level and the serum bactericidal rate. With the help of a severity-of-disease scoring system (APACHE II) the clinical efficacy of antimicrobial therapy was assessed. Eighteen patients were evaluable. The clinical results and the results of the serum assays suggest that treatment with teicoplanin or flucloxacillin, combined with netilmicin, is a safe approach in patients with bacteraemia caused by S. aureus.

Topics: Adult; Cloxacillin; Drug Therapy, Combination; Floxacillin; Glycopeptides; Humans; Microbial Sensitivity Tests; Netilmicin; Sepsis; Staphylococcal Infections; Teicoplanin

Seventy patients with culture-proven bacteremia with gram-negative rods were randomly treated with either a single (S) dose daily or multiple (M) doses daily of netilmicin. All bacterial strains were susceptible to the antibiotic. No differences were found with respect to efficacy. Therapy for bacteremia failed in two M patients, but bacteria persisted in 17 (10 S, 7 M) at the primary infection site. In 12 there was an anatomic or physiologic factor contributing to this persistence. One S patient showed mild nephrotoxicity, but ototoxicity was not found in any of the 35 patients who underwent serial audiography. Mild reversible rises of transaminases were found in 5 of 35 S patients and in 3 of 34 M patients. Once-daily administration of netilmicin seems to be as effective and as safe as conventional multiple daily doses.

Topics: Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Netilmicin; Random Allocation; Sepsis

Rapid eradication of bacteria in bloodstream is critical for the outcome in neonatal bacterial sepsis. Two groups of neonates with E. coli K1 sepsis without purulent meningitis were studied. Group I (n = 14) received cefotaxime IV (100 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1); group II (n = 8) received amoxicillin/clavulanic acid IV (100/10 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1). Both groups were identical. For all strains MICs of cefotaxime, amoxicillin/clavulanic acid, netilmicin were less than 0.2, 4 and 1 mg/l respectively. Serum bactericidal activity (SBA) was determined for each patient (peak sample). The SBA was defined as the greatest dilution in which 99,99% of the inoculum was killed. Time-kill curves were performed with 1:16 dilutions of peak serum samples to measure the kinetic of bacterial killing. The minimal bactericidal time of serum (MBTS) was defined as the minimal time required to observe a decrease of more than 4 log CFU/ml of the bacterial inoculum. Samples (10 microliters) were taken at 1 h intervals over a 6 h period and at 24 h for quantitative culture. All patients cured. Median SBA were respectively 1/128 and 1/64 for group I and II. However, mean MBTS for groups I and II were respectively 1.2 h +/- 0.8 and 3.9 h +/- 1.4. Killing was more rapid in group I (p less than 0.01). The MBTS may be a clinically useful adjunctive test when optimal therapy would be expected.

Topics: Amoxicillin; Blood Bactericidal Activity; Cefotaxime; Clavulanic Acids; Drug Therapy, Combination; Escherichia coli Infections; Humans; Infant, Newborn; Netilmicin; Sepsis; Time Factors

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; beta-Lactamase Inhibitors; Child; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Netilmicin; Neutropenia; Penicillins; Retrospective Studies; Sepsis; Ticarcillin; Tobramycin

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.

Topics: Adolescent; Adult; Bacterial Infections; Cefotaxime; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Netilmicin; Random Allocation; Sepsis; Staphylococcal Infections

In a prospective randomized double-blind study of 141 patients referred for reconstructive vascular surgery on the abdominal aorta and the lower extremities, placebo was compared to antibiotic prophylaxis. The prophylaxis group received three doses of a combination of methicillin, 2 g and netilmicin, 200 mg. Antibiotic prophylaxis reduced postoperative wound infections as compared to placebo, i.e. 4/69 (5.8%) vs. 12/72, (16.7%) respectively (P = 0.04). No graft infections occurred. Two cases of postoperative septicaemia were seen in the placebo group, none in the antibiotic group. Among different procedures aortic-femoral bypass operations showed the highest wound infection rates. The two treatment groups were comparable with regard to all other postoperative complications registered, including nephro- and ototoxicity. The antibiotic regimen was considered safe, but had only marginal value as prophylaxis in vascular reconstructive surgery on the abdominal aorta and the lower extremities.

Topics: Adolescent; Adult; Aged; Aorta, Abdominal; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Methicillin; Middle Aged; Netilmicin; Postoperative Complications; Premedication; Sepsis; Surgical Wound Infection; Vascular Surgical Procedures

The aim of this study was to compare the prophylactic effects of netilmicin plus metronidazole administered for one day and of doxycycline administered for five days on the incidence of postoperative sepsis in patients undergoing elective colorectal surgery. One hundred patients were studied, 50 men and 50 women, with a mean age of 66.6 years. The patients were randomized into the two groups. Wound infections occurred in a total of 9 patients, 5 in the doxycycline group and 4 in the group given netilmicin plus metronidazole, i.e. the overall infection rate was 9%. It is concluded that there is no statistically significant difference on the incidence of postoperative wound sepsis in patients undergoing elective colorectal surgery between the group given doxycycline for five days and the group given netilmicin plus metronidazole for one day.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Colon; Doxycycline; Female; Humans; Male; Metronidazole; Middle Aged; Netilmicin; Postoperative Complications; Rectum; Sepsis; Surgical Wound Infection

Fifty-nine patients with severe urinary tract infections were treated with either cefotaxime or ampicillin plus netilmicin in a controlled, open randomised study of the clinical and bacteriological effects. The patients responded favourably in both groups. The minimum inhibitory concentrations of cefotaxime against the isolates from blood were low for all bacterial strains except one (Streptococcus faecalis). Time to normalisation of temperature was significantly shorter in the cefotaxime group. The results suggest that cefotaxime is an effective and well-tolerated agent in the treatment of serious infections. However, the difference between the two groups was too small to allow preference of one procedure over the other.

Topics: Ampicillin; Cefotaxime; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Sepsis; Surgical Wound Infection; Urinary Tract Infections

During a randomized clinical trial comparing tobramycin plus ticarcillin to netilmicin plus ticarcillin as empiric therapy of febrile neutropenic patients, Staphylococcus epidermidis emerged as the predominate superinfecting pathogen in tobramycin recipients. Overall clinical response was 68% (44/65 responding) in tobramycin/ticarcillin recipients and 73% (45/62) in netilmicin/ticarcillin recipients. However, 5/65 tobramycin/ticarcillin treated episodes were complicated by bacteremic superinfection with Staphylococcus epidermidis, as compared to 0/62 netilmicin/ticarcillin treated episodes (p less than 0.05). Four of the five bacteremic strains produced aminoglycoside adenylating enzyme ANT 4', 4''. Prior colonization of patients with identical strains was demonstrated by plasmid profile analysis, antibiograms and biotyping with the API Staph-Ident system. During the trial, 36 consecutive patients were studied for colonization patterns with coagulase-negative staphylococci. S. epidermidis accounted for 566/831 (68%) isolates of coagulase-negative staphylococci recovered from surveillance cultures. Tobramycin-resistant strains were acquired in 2/17, 4/12 and 9/14 patients during trimethoprim/sulfamethoxazole, netilmicin/ticarcillin and tobramycin/ticarcillin therapy, respectively. Prior to aminoglycoside therapy, 77% of strains were susceptible to less than or equal to 8 micrograms/ml of tobramycin, but only 35% and 28% were susceptible to tobramycin after initiation of tobramycin/ticarcillin and netilmicin/ticarcillin therapy, respectively. In contrast, greater than or equal to 93% of isolates were susceptible to netilmicin before and after aminoglycoside therapy. Absence of several sites susceptible to modification by aminoglycoside inactivating enzymes produced by staphylococci may give netilmicin a therapeutic advantage in the therapy of febrile neutropenic patients.

Topics: Adult; Agranulocytosis; Aminoglycosides; Clinical Trials as Topic; Cross Infection; Drug Therapy, Combination; Ear; Humans; Kidney; Netilmicin; Neutropenia; Penicillin Resistance; Random Allocation; Sepsis; Staphylococcal Infections; Staphylococcus epidermidis; Ticarcillin; Tobramycin

Fifty patients with acute non-lymphocytic leukaemia were treated by random allocation with either ceftazidime alone or a combination of piperacillin, netilmicin and cefotaxime for 65 febrile neutropenic episodes. Nineteen of 33 patient episodes (58%) responded to ceftazidime alone compared with 21 of 32 episodes (66%) treated with the combination. There was one infective death in a patient given the combination; rates of documented superinfection were low. The treatment groups appeared identical in terms of patient demography, underlying disease and other risk factors, though patients with a clinical site of infection responded more slowly than those without. Bacteraemia per se did not appear to influence outcome. Bactericidal serum concentrations greater than or equal to 8 X the minimum bactericidal concentration were predictive of a rapid response (within 4 days) to antibiotics. Furthermore, serum from patients treated with ceftazidime maintained adequate cidal activity against Pseudomonas aeruginosa for longer than that obtained from patients treated with the three-drug combination. Ceftazidime was shown to be a safe and effective alternative to the three-drug combination for the initial management of febrile neutropenic episodes in leukaemic patients.

Topics: Adolescent; Adult; Bacterial Infections; Cefotaxime; Ceftazidime; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Netilmicin; Neutropenia; Penicillin Resistance; Piperacillin; Random Allocation; Sepsis

A prospective randomised controlled trial of mezlocillin versus netilmicin in 133 patients undergoing biliary surgery at a district hospital is reported. Sixty-four patients received mezlocillin and 69 received netilmicin. The two groups of patients were comparable with regard to age, sex, underlying pathology and operative procedures performed. The incidence of infected bile at operation was 14.2% and both antibiotics were equally effective in reducing postoperative bacteraemia (0.75%) and wound infection (4.5%) to acceptable levels. It is concluded that netilmicin is a more cost-effective antibiotic in biliary surgery than mezlocillin.

Topics: Aged; Bacteria; Bile; Biliary Tract Surgical Procedures; Clinical Trials as Topic; Female; Humans; Male; Mezlocillin; Middle Aged; Netilmicin; Prospective Studies; Random Allocation; Sepsis; Surgical Wound Infection

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: Agranulocytosis; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Drug Therapy, Combination; Gentamicins; Humans; Netilmicin; Neutropenia; Sepsis

Eighty patients were treated with either amikacin or netilmicin in a prospective randomized study of serious gram-negative bacillary infections, including 11 due to gentamicin-resistant pathogens. Thirty-six treated with netilmicin and 35 treated with amikacin were evaluable for efficacy or toxicity, or both. The overall groups differed significantly only in age. There were no significant differences in efficacy of the two drugs. There were no statistically significant differences at the 95% level between the netilmicin group and the amikacin group with respect to nephrotoxic reactions (38 versus 28%, respectively) or ototoxic reactions (9 versus 25%, respectively). Further comparative trials of netilmicin and other aminoglycosides appear warranted before it is widely used.

Topics: Adult; Aged; Amikacin; Bacterial Infections; Clinical Trials as Topic; Drug Resistance, Microbial; Female; Gentamicins; Humans; Kanamycin; Lung Diseases; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

Aminoglycosides are commonly used antibiotics with excellent renal parenchymal penetration. Their clinical effectiveness is counter balanced with the risk of renal toxicity, which develops in a dose-dependent fashion. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome (BLS), or distal renal tubular acidosis.(1-4) Although tubulopathy associated with amikacin and gentamicin was reported in adults and rarely children, to the best of our knowledge, netilmicin-associated BLS neither in adults nor in children has been reported in the literature. We here report a 30-week, 770 g male preterm infant who developed BLS just after netilmicin treatment for neonatal sepsis and recovered 6 weeks after the drug cessation.

Topics: Adult; Anti-Bacterial Agents; Bartter Syndrome; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Netilmicin; Pregnancy; Sepsis

The aim of this study was develop an optimal dosing regimen for netilmicin in neonates.. This was a population pharmacokinetic study in 97 neonates aged from 2 to 28 days after the due date who were being treated with netilmicin for suspected sepsis. The model was used to simulate dosing regimens.. The principle factors influencing netilmicin clearance (CL) were postmenstrual age (PMA) and current body weight (CWT), and the principal determinant of volume of distribution (V) was CWT. The final covariate model was CL = 0.192 x (CWT/2)(1.35) x (PMA/40)(1.03), V = 1.5 x (CWT/2)(0.3). The optimal dosing was 5 mg/kg ever 36 h, 5 mg/kg every 24 h, 6 mg/kg every 24 h and 7 mg/kg every 24 h for neonates < or =27, 28-30, 31-33 and > or =34 weeks PMA, respectively.. Individualisation of netilmicin dosing in neonates requires adjustment of dose by body weight, and dosing interval by both PMA and CWT.

Topics: Anti-Bacterial Agents; Apgar Score; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gestational Age; Humans; Infant, Newborn; Infusions, Intravenous; Male; Medical Records; Metabolic Clearance Rate; Models, Biological; Netilmicin; Predictive Value of Tests; Retrospective Studies; Sepsis

Topics: Amikacin; Anti-Bacterial Agents; Drug and Narcotic Control; Humans; Infant, Newborn; Medical Audit; Netilmicin; New Zealand; Retrospective Studies; Sepsis; Staphylococcal Infections; Streptococcal Infections; Streptococcus agalactiae; Treatment Failure

To determine the effect of aminoglycoside cycling in six tertiary intensive care units (ICU) on the rates of sepsis, aminoglycoside resistance patterns, antibiotic consumption, and costs.. This was a prospective longitudinal interventional study that measured the effect of change from first-line gentamicin usage (February 2002-February 2003) to amikacin usage (February 2003-February 2004) on the aminoglycoside resistance patterns, number of patients with gram-negative bacteremia, consumption of antibiotics, and the cost of antimicrobial drugs in 6 tertiary care ICUs in Zagreb, Croatia.. The change from first-line gentamicin to amikacin usage led to a decrease in the overall gentamicin resistance of gram-negative bacteria (GNB) from 42% to 26% (P<0.001; z-test of proportions) and netilmicin resistance from 33% to 20% (P<0.001), but amikacin resistance did not change significantly (P=0.462), except for Acinetobacter baumanni (P=0.014). Sepsis rate in ICUs was reduced from 3.6% to 2.2% (P<0.001; chi(2) test), with a decline in the number of nosocomial bloodstream infections from 55/100 patient-days to 26/100 patient-days (P=0.001, chi(2) test). Furthermore, amikacin use led to a 16% decrease in the overall antibiotic consumption and 0.1 euro/patient/d cost reduction.. Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin, the number of GNB nosocomial bacteremias, and the cost of total antibiotic usage in ICUs.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Cost-Benefit Analysis; Croatia; Drug Resistance, Multiple, Bacterial; Gentamicins; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Longitudinal Studies; Netilmicin; Prospective Studies; Sepsis

Once-daily administration of aminoglycoside antibiotics has become the most acceptable dosing schedule for the majority of patients. There are few published data on the impact of post-natal age on aminoglycoside concentrations in preterm infants receiving once-daily dosage regimens. Netilmicin was administered as a once-daily dose of 4 mg/kg. In 141 episodes of suspected sepsis in 123 babies, trough netilmicin concentrations ranged from undetectable to 4.0 mg/l. Netilmicin concentrations were above a level of 2 mg/l in 10.6% of episodes. Netilmicin concentrations decreased with increasing post-natal age and weight. Levels were higher in males compared to females. Increased creatinine concentrations were associated with higher netilmicin concentrations. This study emphasises the importance of post-natal age as a determinant of aminoglycoside concentrations with a once-daily dosing regimen in a neonatal intensive care population. Trough levels should be carefully monitored and consideration given to extending dosage intervals particularly when netilmicin is administered once daily to preterm infants in the first week of life.

Topics: Aging; Anti-Bacterial Agents; Audiology; Body Weight; Creatinine; Enterobacteriaceae Infections; Enterococcus; Escherichia coli Infections; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Intensive Care, Neonatal; Linear Models; Male; Netilmicin; Retrospective Studies; Sepsis; Staphylococcal Infections; Streptococcal Infections

The pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) was studied in 16 neonates, divided for analysis into three groups according to gestational age: group 1 >36 weeks (n=7); group II between 34-36 weeks (n=4); and group III <34 weeks (n=5). The serum netilmicin (mean +/- SD) 4h and 24h after the first dose were 4.7 +/- 0.8 and 0.8 +/- 0.5 mg/L; 4.9 +/- 0.8 and 1.9 +/-0.2 mg/L; 4.9 +/- 0.5 and 1.7 +/- 0.5 mg/L in groups I, II and III respectively. After the second dose, concentrations at 2, 4, 8, 16 and 24 h were 7.2 +/- 1.0, 5.0 +/- 0.8, 3.0 +/- 0.6, 1.7 +/- 0.4 and 0.9 +/- 0.2 mg/L (group I); 8.6 +/- 0.2, 6.1 +/- 0.5, 4.2 +/- 0.7, 2.6 +/- 0.1 and 1.4 +/- 0.4 mg (group II); 9.0 +/- 1.2, 6.3 +/- 0.9, 4.1 +/- 0.7, 2.6 +/- 0.5 and 1.7 +/- 0.3 mg/L (group III). There was a large degree of inter-patient variability in serum concentrations and serum half-life (t1/2), volume of distribution (VD), area-under-the-curve (AUC), relative serum clearance (Clp) such that these parameters could not be correlated to age or weight. Absolute serum clearance (L/h) was correlated with gestational age (r = 0.672, P <0.01). There was no statistically significant evidence of accumulation between the first and second doses for any patient group. One baby from each group II and group III had concentration >2 mg/L 24h after the first dose and one baby from group III had concentration >2 mg/L 24h after the second dose. There are no established correlations between serum netilmicin concentrations and efficacy or toxicity in neonates and keeping 24 h trough concentration below 2 mg/L with a once-a-day dose of 4.5 mg/L would have to be validated in terms of its clinical efficacy and potential toxicity in a neonatal population.

Topics: Drug Administration Schedule; Gentamicins; Gestational Age; Humans; Infant, Newborn; Netilmicin; Sepsis; Time Factors

Topics: Animals; Anthrax; Bacillus anthracis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Netilmicin; Penicillin G; Sepsis; Sutures; Umbilicus; Wool

The aim of the study was to investigate the in vitro antibiotic susceptibility of blood culture isolates after almost 20 years with ampicillin and methicillin as empirical treatment for neonatal septicaemia. All blood culture isolates and their antibiograms obtained in a single tertiary neonatal intensive care unit from 1 January 1989 to 31 December 1994 were reviewed. Two hundred and six blood cultures from 181 infants containing 223 bacterial and 11 fungal isolates were identified during 4416 admissions. Fifteen (6.7%) of the bacterial isolates were resistant to ampicillin and netilmicin. Fourteen per cent of the staphylococcal spp. were susceptible to penicillin while more than 90% were susceptible to netilmicin. The coagulase-negative staphylococci (CONS) were resistant to netilmicin, methicillin and gentamicin in 12%, 49% and 65%, respectively. Eighty-nine per cent of the methicillin-resistant CONS were susceptible to netilmicin as opposed to 17% to gentamicin (p<0.001). Except for one strain of Acinetobacter sp., all Gram-negative bacteria were susceptible to netilmicin. Our data show that the ampicillin-netilmicin combination still provides a high in vitro coverage (93%) against bacteria identified in blood cultures from newborns in our unit. Netilmicin has a significantly better in vitro effectiveness against CONS than gentamicin.

Topics: Ampicillin; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Netilmicin; Sepsis

Topics: Anti-Bacterial Agents; Ceftazidime; Drug Therapy, Combination; Humans; Liver Cirrhosis; Netilmicin; Sepsis

The most common organisms in neonatal meningitis are group B streptococcus and Gram negative enteric bacteriae. Although Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are the most frequent causes of meningitis in infancy and childhood, they are uncommon in newborns. We report one case of neonatal meningitis and maternal septicemia.

Topics: Ampicillin; Female; Gentamicins; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Meningitis, Pneumococcal; Netilmicin; Penicillins; Pneumococcal Infections; Puerperal Infection; Sepsis; Serotyping; Streptococcus pneumoniae

A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.

Topics: Acyclovir; Alanine Transaminase; Aspartate Aminotransferases; Bicarbonates; Cloxacillin; Dopamine; Female; Fetal Hypoxia; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature, Diseases; Liver; Male; Necrosis; Netilmicin; Pancuronium; Partial Thromboplastin Time; Penicillins; Pregnancy; Prothrombin Time; Sepsis; Shock; Sodium; Sodium Bicarbonate

A total of 790 blood culture isolates was collected during 3 study periods in 1982/83, 1984/85 and 1987/88. Staphylococci were the most frequent bacteria in the first two periods (56.5% and 63%, respectively). During the last period, E. coli was the most frequent of all species (27%). Differences in the distribution of bacteria between the laboratories were considerable. In one laboratory in Vienna, coagulase-negative staphylococci dominated in all 3 study periods (32%, 33% and 47%). Susceptibility against gentamicin, tobramycin and netilmicin (MIC less than or equal to 4 mg/l), as well as against amikacin (MIC less than or equal to 8 mg/l) were determined by a microdilution method. The resistance rates against gentamicin (G) were 25%, 21% and 25%, against tobramycin (T) 27%, 19% and 25%, against netilmicin (N) 6%, 4% and 19%, and against amikacin (A), 5%, 2% and 19%. Most resistant strains were staphylococci (G 26%-41%, T 26%-46%, N 3%-31%, A 3%-36%), whereas gram-negative bacilli were more susceptible (G 12%-14%, T 7%-11%, N 7%-9%, A 1%-7.5%). The increase of resistance against netilmicin and amikacin in staphylococci was most striking. Nearly all those strain could be attributed to one laboratory in Vienna. Most of them were coagulase-negative staphylococci. In the first study period, the most frequent pattern was resistance against gentamicin and tobramycin, whereas in the last period resistance to all 4 aminoglycosides dominated. The study demonstrates considerable local differences in antibiotic resistance. Monitoring of antibiotic resistance in collaborative studies using standardized methods should be a valuable tool in planning strategies for controlling an epidemic spread of resistance.

Topics: Amikacin; Anti-Bacterial Agents; Austria; Drug Resistance, Microbial; Enterobacteriaceae; Escherichia coli; Gentamicins; Gram-Negative Bacteria; Humans; Netilmicin; Pseudomonas aeruginosa; Sepsis; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Tobramycin

Pharmacokinetic profiles in small animals substantially differ from those observed in man. We hence devised a man adapted animal model to critically assess the impact of such differences on antimicrobial efficacy. We approximated in mice the human pharmacokinetic profiles of netilmicin, ticarcillin and ceftazidime. The CD50 (curative dose for 50% of lethally intra-peritoneally infected animals) against Pseudomonas aeruginosa was comparatively determined for murine versus man-adapted pharmacokinetic profiles. With netilmicin the man-adapted profile was significantly less efficacious than the murine profile. In contrast, a significant superiority of the man-adapted profile was found with the beta-lactam drugs. We conclude that determinations of antimicrobial activity in small animals may yield misleading results in respect to man. Depending on the drug in question, murine pharmacokinetics may lead to overestimation or underestimation of antimicrobial activity. Our findings are of particular importance for the interpretation of studies in small animals comparing different antimicrobial compounds or different dosage regimens.

Topics: Animals; Ceftazidime; Disease Models, Animal; Drug Administration Schedule; Female; Half-Life; Injections, Subcutaneous; Mice; Mice, Inbred ICR; Netilmicin; Peritonitis; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Sepsis; Specific Pathogen-Free Organisms; Ticarcillin

A 20-year-old primigravida in the 33rd week of gestation was delivered of a girl weighing 1,790 g 23 h after spontaneous rupture of the membranes. 13 h after birth, the child showed signs of shock. Cultures of blood, conjunctiva and nasopharyngeal aspirate grew Streptococcus pneumoniae of serotype 11. Cultures from the mother's cervix and from the placenta and membranes also grew S. pneumoniae of the same serotype. The infant responded well to ampicillin and netilmicin. The early-onset pneumococcal septicemic cases reported over the last 20 years are reviewed.

Topics: Adult; Ampicillin; Cervix Uteri; Female; Humans; Infant, Newborn; Netilmicin; Placenta; Pneumococcal Infections; Pregnancy; Risk Factors; Sepsis; Serotyping; Streptococcus pneumoniae

Topics: Ampicillin; Drug Resistance, Microbial; Drug Therapy, Combination; Enterococcus faecalis; Humans; Infant; Male; Netilmicin; Sepsis; Streptococcal Infections; Vancomycin

Thirteen episodes of fever in bone marrow transplantation recipients (23 months to 11 years old children) were treated by ceftazidime (100-200 mg/kg/j) and netilmicin (7 mg/kg/j). Vancomycin was added at the 24th hour in 10 cases of persistent fever. 6 presumed agents of infection were isolated before antibiotic treatment: blood cultures (streptococci 2, staphylococcus 1, proteus 1), fecal sample (E. coli 1), urine (E. coli 1). Modifications of aerobic fecal flora were studied under this treatment. E. coli, staphylococci and enterococci were the mainly strains isolated. There were no third generation cephalosporins resistant Gram-negative bacteria. High level resistance to aminoglycosides was observed in enterococcal strains, isolated during and after treatment. Ceftazidime-netilmicin (+/- vancomycin) was an effective and safe combination for the management of febrile neutropenic episodes.

Topics: Bacteria; Bacterial Infections; Bone Marrow Transplantation; Ceftazidime; Child; Child, Preschool; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Netilmicin; Postoperative Complications; Sepsis; Time Factors; Vancomycin

Sixty infections episodes in granulocytopenic patients have been treated in first line with a piperacillin and netilmicin combination. Treatment has been successful in 78% bacterial infections. So, this antibiotic combination appears as a very effective therapy of infection in neutropenic patients.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Piperacillin; Sepsis

The pharmacokinetics of ceftazidime and netilmicin were evaluated under septicemic conditions. In a longitudinal study, both drugs were administered simultaneously (ceftazidime 2.0 g 20 min constant i.v. infusion and netilmicin 150 mg i.v. bolus injection) every 12 hours to patients who had a positive blood culture and hyperdynamic circulatory functions. Twenty-four hours after the first period of this pharmacokinetic study, identical parameters were evaluated under dipyrone induced normothermic conditions. The mean residence time and the volume of distribution was significantly altered during septicemia compared to normal conditions. With respect to the relative distribution properties ceftazidime tended to be distributed to a greater extent to the tissue compartment, whereas netilmicin showed an opposite behaviour. Beside significant correlations of absolute values, i.e. blood volume vs. volume of distribution, and relative values, i.e. total peripheral resistance vs. extraction rate, all other attempts failed to show any meaningful correlation. Owing to the heterogenous alterations of metabolic and hemodynamic functions and pharmacokinetic parameters, respectively, the data gained from this study do not allow any statistically validated conclusion regarding the pathophysiological mechanisms involved, although these findings are in accordance with animal experiments.

Topics: Adolescent; Adult; Body Temperature; Ceftazidime; Dipyrone; Female; Hemodynamics; Humans; Kidney Function Tests; Kinetics; Liver Function Tests; Longitudinal Studies; Male; Middle Aged; Netilmicin; Sepsis

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.

Topics: Amikacin; Anti-Bacterial Agents; Bacteria; Bacteriuria; Drug Resistance, Microbial; Escherichia coli; Europe; Gentamicins; Humans; Netilmicin; Pseudomonas; Sepsis; Staphylococcus; Tobramycin

Topics: Animals; Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Humans; Longitudinal Studies; Netilmicin; Rabbits; Sepsis

A 59-year-old man developed septicaemia caused by Kingella denitrificans. Treatment was with ampicillin and an aminoglycoside. The illness was complicated by a cerebral embolus. An obvious source of infection was not found.

Topics: Ampicillin; Endocarditis, Bacterial; Gram-Negative Aerobic Bacteria; Humans; Male; Middle Aged; Neisseriaceae; Netilmicin; Sepsis

The purpose of this study was to evaluate the in vitro synergism between piperacillin and netilmicin against microorganisms isolated from Danish patients with septicemia and to examine the influence of inactivation of piperacillin among these bacteria on the synergy results. A total of 132 stains was examined: Escherichia coli 20, indole-positive Proteus 17, Klebsiella pneumoniae 18, Enterobacter cloacae 20, Pseudomonas aeruginosa 20, Staphylococcus aureus 20, and coagulase-negative staphylococci 17. Synergy testing was performed by checkerboard titration in microtiter trays. The ability of the strains to inactivate piperacillin was examined by the clover-leaf test. Synergism was found for 52% of the strains and partial synergism for 32%. Antagonism was not found. Of the piperacillin-resistant strains synergism could be demonstrated in 80% compared with 33% of the piperacillin-susceptible strains (p less than 0.001). No significant correlation was seen between the results of the synergy test and the results of the susceptibility test to netilmicin. The frequency of piperacillin inactivation according to the clover-leaf test was significantly higher among the strains with synergism than among all the others (p less than 0.02). The combination of piperacillin and netilmicin gave good results concerning the in vitro synergism. This synergism was probably sometimes caused by netilmicin disturbing the bacterial production of piperacillin-inactivating proteins.

Topics: Bacteria; Drug Synergism; Enterobacter; Escherichia coli; Humans; Klebsiella; Microbial Sensitivity Tests; Netilmicin; Piperacillin; Pseudomonas aeruginosa; Sepsis; Staphylococcus aureus

The emergence of ampicillin and chloramphenicol resistant Haemophilus influenzae type b in Denmark has created demands for alternative treatments of serious infections with H. influenzae. In this study 102 strains of H. influenzae recovered from cerebrospinal fluid (85) and blood (17) were tested for susceptibility to ampicillin, piperacillin, erythromycin, rifampicin, chloramphenicol, cefuroxime, cefotaxime, ceftazidime, ceftriaxone, moxalactam, aztreonam, and netilmicin by means of the agar dilution method. The majority (97%) was H. influenzae type b and of these strains 94% belonged to biotype I. Nine of the investigated strains were beta-lactamase producers. Ceftriaxone and cefotaxime were the most active agents (MIC90 less than or equal to 0.025 microliter/ml) followed by moxalactam and aztreonam (MIC90 = 0.1 microgram/ml). Except for ampicillin and piperacillin, the MIC was similar for beta-lactamase producers and non-producers. Several of the investigated antibiotics, especially some of the third generation cephalosporins, might constitute valid therapeutical alternatives to conventional drugs in the treatment of severe H. influenzae infections.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Chloramphenicol; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Netilmicin; Rifampin; Sepsis

The effectiveness of netilmicin was evaluated retrospectively in 40 patients with culture-documented bacteremia due to Pseudomonas aeruginosa. Netilmicin was the only antibiotic active in vitro against P aeruginosa that was administered to these patients. In 18 patients, Pseudomonas bacteremia developed in association with a Pseudomonas infection of the urinary tract; in 22 patients, Pseudomonas bacteremia developed from nonurinary or unknown sources. A clinical resolution or improvement was observed in 92% of the evaluable patients, and P aeruginosa was eliminated from the blood of 90% of the patients. The drug had nephrotoxic effects in two patients, but in no patient was there subjective or audiometric evidence of ototoxic effects. Three patients died during therapy. Based on these data, netilmicin is effective, and is associated with a low incidence of toxic effects, in the treatment of patients with Pseudomonas bacteremia.

Topics: Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Netilmicin (NTL), a new semisynthesized aminoglycoside, was evaluated in 11 episodes of infection in 10 patients, who had severe underlying diseases, such as acute myocardial infarction, cerebral infarction, malignancy and hepatic cirrhosis. The infection was bacteremia in 3 cases, urinary tract infections in 3 cases and respiratory tract infections in 5 cases. NTL was administered intramuscularly at a dose of 100 mg twice a day for 3 to 14 days. Overall clinical efficacy was only 40%, including excellent in 2 cases, good in 2 cases, fair in 3 cases and poor in 3 cases. Bacteriologically, 2 episodes of E. coli, 2 of S. marcescens and 1 of K. pneumoniae were eradicated, whereas, 2 of P. aeruginosa were decreased, and 1 of K. pneumoniae and 1 of P. rettgeri were persisted. Transient eosinophilia was observed in 1 case, and also nephrotoxicity was encountered in 1 case.

Topics: Aged; Bacteria; Drug Evaluation; Drug Resistance, Microbial; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Respiratory Tract Infections; Sepsis; Urinary Tract Infections

29 patients with serious renal or urinary tract infections were treated with netilmicin (initial dose 1.5 mg/kg twice daily). All but two patients were bacteriologically cured and responded well clinically. 13 patients with initial renal impairment were analysed separately. Whereas the patients with initial normal renal function did not show any increase of serum creatinine levels during and after treatment, the patients with renal impairment showed a significant increase of serum creatinine during the course of treatment, but no clinical signs of renal function deterioration. During the follow-up period (18 months), serum creatinine values in all cases but one returned to the pretreatment levels. Thus, the investigation revealed that netilmicin had a good clinical and bacteriological effect without signs of persistent renal damage.

Topics: Adult; Aged; Creatinine; Female; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Pyelonephritis; Renal Dialysis; Sepsis; Urinary Tract Infections

Thirty neonates and infants have been treated for verified or suspected infections with a combination of netilmicin and ampicillin intravenously for 7 days. The infecting organisms were isolated in 18 patients, of whom 2 had osteomyelitis and 2 had pneumonia. In 3 cases of pneumonia and 9 cases of suspected septicaemia bacteriological cultures were negative. None of the children died, and in all but the 2 cases of osteomyelitis, therapy led to complete resolution of the signs of infection and recovery without sequelae. No adverse reactions to antibiotic therapy were recorded. Upon follow-up examinations at the age of 3 months there has been no sign of auditory impairment as assessed by Brain Stem Evoked Response. Netilmicin is thus tolerated well in neonates and infants, and when guided by serum concentrations considered to be a safe and reliable aminoglycoside.

Topics: Drug Evaluation; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Netilmicin; Osteomyelitis; Sepsis; Staphylococcal Infections; Streptococcal Infections

25 patients were treated with netilmicin because of suspected or verified septicaemia or other severe infections. Netilmicin was administered intramuscularly in a dose of 2 mg/kg body weight every 8 hours. For patients with elevated plasma creatinine the dosage was reduced according to the degree of elevation. Average length of treatment was 7 days (3-12 days). In 22 patients all symptoms and signs of infection disappeared. In one patient antibiotic treatment had to be changed and in two patients abscesses had to be surgically drained. Kidney function was monitored during and after treatment by plasma creatinine measurements and 51Cr-EDTA clearance. Netilmicin was discontinued in 4 patients because of an increase in plasma creatinine but little or no drug related nephrotoxicity was observed. Audio-vestibular function was monitored during and after treatment. Netilmicin was discontinued in one patient because of slight subjective loss of hearing. Subsequent audio-vestibular examination was normal.

Topics: Adult; Aged; Creatinine; Dizziness; Drug Evaluation; Female; Gentamicins; Hearing Loss; Humans; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

Sixteen patients with chronic or recurrent urinary tract infections, 14 with septicaemia, 2 with salmonellosis, 2 with pneumonia and 1 with acute mastitis were treated with 200 mg (2.2-3.6 mg/kg) netilmicin intramuscularly every 8 hours for 7-10 days (mean 8.8 days). 28 patients were cured, 5 showed marked improvement and 2 patients with septicaemia and severe underlying diseases failed to respond to treatment. The bacterial isolates were inhibited by 4.0 mg netilmicin/l or less. Antibiotic serum level determinations were performed in 32 patients. Mean serum concentrations of netilmicin 1 and 8 hours after injection were 12.6 and 2.0 mg/l respectively in 27 patients with normal serum creatinine levels. In 5 patients with elevated serum creatinine, mean peak and trough values were 21.5 and 5.8 mg/l, respectively. Mean netilmicin concentrations in serum and skin blister fluid obtained from 4 patients were equal 2-3 hours after injection, indicating appropriate tissue penetration. Nephrotoxicity occurred in 2 patients. Ototoxicity was not demonstrated. Netilmicin appears to be an effective and safe drug in the treatment of a variety of bacterial infections.

Topics: Adult; Aged; Bacterial Infections; Chronic Disease; Creatinine; Drug Evaluation; Female; Gentamicins; Hearing; Humans; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

49 newborns and infants were treated with netilmicin for verified or suspected infections. Infection was verified in 23 patients (mean gestational age 32 weeks and mean body weight 2100 g) and clinical cure or marked improvement occurred in 20 of these. Of the remaining 3 patients, 2 died, partly due to reasons unassociated with infection. 25 causative organisms were isolated and bacteriological elimination was achieved in 73% of the cases. At an average dose of 2.6 mg/kg twice a day, peak serum concentrations (30 min following injection) were 7.4 +/- 3.4 micrograms/ml. Serum half life was approximately 4.5 hours for infants born at term, and longer at shorter gestational age. Netilmicin is considered a safe and efficient aminoglycoside with a low rate of adverse effects.

Topics: Bacterial Infections; Drug Evaluation; Escherichia coli Infections; Female; Gentamicins; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Klebsiella Infections; Male; Netilmicin; Sepsis; Staphylococcal Infections; Streptococcal Infections

Netilmicin, a new semisynthetic aminoglycoside, was evaluated in the therapy of 33 episodes of infection in 30 patients. Eighteen patients had documented bacteremia. Infection sites included pulmonary, urinary tract and soft tissue areas. A complete bacteriologic and clinical cure rate of 85 per cent was achieved. No treatment failures occurred in the bacteremic group. Although netilmicin is less effective than gentamicin in vitro against Pseudomonas, it was clinically and bacteriologically effective. Netilmicin bacteriologic cures occurred in patients whose organisms were inhibited by 6.2 microgram/ml or less of netilmicin. Despite a uniform dosing protocol, a wide range of netilmicin serum levels was obtained. Adverse effects were limited to one case of transient nephrotoxicity and one Candida urinary suprainfection. Netilmicin appears to be an effective, safe agent for the therapy of serious infections.

Topics: Adult; Aged; Amikacin; Bacterial Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

Topics: Adult; Aged; Drug Resistance, Microbial; Enterobacteriaceae Infections; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Urinary Tract Infections