netilmicin and Enterobacteriaceae-Infections

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

A double-blind, randomized study of gentamicin and netilmicin, each in combination with cefoxitin, was done to compare their respective efficacy and toxicity in patients with serious systemic infection. Thirty-seven surgical patients were evaluated for efficacy and 46 patients were evaluated for toxicity. The most frequently cultured organisms were Escherichia coli (15), Klebsiella sp (9), Proteus sp (6), and Bacteroides sp (4). For 23 patients treated with gentamicin-cefoxitin (G-C), the clinical response was favorable in 20/21 (95.2%) evaluable cases, and elimination or marked reduction of 33/34 (97.1%) organisms was achieved. For 14 patients treated with netilmicin-cefoxitin (N-C), the clinical response was favorable in 13/13 (100%) evaluable cases, and 19/20 (95%) organisms were eliminated or markedly reduced. Nephrotoxicity was defined as an increase in serum creatinine to greater than 25% over baseline with an absolute rise of at least 0.5 mg/100 ml to a value greater than or equal to 1.3 mg/100 ml. Based on these criteria, nephrotoxicity was seen in 2/27 (7.4%) patients treated with G-C and in 3/19 (15.8%) patients treated with N-C. Ototoxicity was defined as a greater than 20 dB loss at any frequency. Based on these criteria, ototoxicity was seen in 5/27 (18.5%) patients treated with G-C and 2/19 (10.5%) patients treated with N-C. The data show no significant difference in toxicity and suggest that netilmicin and gentamicin are both highly effective in combination with cefoxitin in patients who have serious infections after surgery.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bacteroides Infections; Cefoxitin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Gentamicins; Hearing; Humans; Male; Middle Aged; Netilmicin; Random Allocation; Surgical Wound Infection; Vestibular Function Tests

Topics: Adult; Aged; Bacillus subtilis; Bacteriuria; Clinical Trials as Topic; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pseudomonas Infections

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

Topics: Acute Disease; Aged; Bacteremia; Cefepime; Cephalosporins; Cholangiography; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy; Cholecystitis; Enterobacteriaceae Infections; Gentamicins; Hafnia alvei; Humans; Liver Abscess; Male; Netilmicin; Suppuration; Treatment Outcome

The inhibitory combination effect of cefmenoxime with gentamicin, tobramycin, netilmicin and amikacin against 148 Enterobacteriaceae was compared using the checkerboard agar dilution technique. On average 41% of cefmenoxime-moderately susceptible (MIC between 2 and 32 micrograms/ml) or cefmenoxime-resistant (MIC greater than 32 micrograms/ml) strains were inhibited by synergistic, and 23,5% by partial synergistic cefmenoxime-aminoglycosides combinations. Against cefmenoxime-susceptible strains, these rates of synergy or partial synergy were twofold lower, but only one isolate was not susceptible to these combinations. The amikacin-cefmenoxime interaction was the most performant.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Cefmenoxime; Cefotaxime; Drug Resistance, Microbial; Drug Synergism; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Netilmicin; Species Specificity; Tobramycin

An outbreak of colonisation and infection with a netilmicin resistant strain of Serratia marcescens occurred in a special care baby unit. S marcescens was isolated from a total of 13 babies; significant infection occurred in five, of whom two died. Epidemiological investigation failed to detect a common source but gastrointestinal colonisation of babies formed a prolonged and possibly important reservoir for infection. Containment proved difficult until the unit was closed to new admissions, and even then spread to a temporary unit ensued. O Serotyping and bacteriophage typing disclosed a single epidemic strain. This produced an aminoglycoside acetylating enzyme (AAC(6')) conferring resistance to netilmicin and tobramycin and moderate resistance to amikacin. Use of gentamicin resulted in the isolation of serratia with increased resistance to all aminoglycosides, and, similarly, increased resistance to third generation cephalosporins emerged with their use.

Topics: Acetyltransferases; Amikacin; Cefotaxime; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Netilmicin; Nurseries, Hospital; Serratia marcescens; Tobramycin

Topics: Adolescent; Adult; Aged; Bacterial Infections; Connective Tissue Diseases; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Osteomyelitis; Urinary Tract Infections

Most (76%) of the 284 gentamicin-resistant Enterobacteriaceae isolated from patients hospitalised in Eindhoven or its vicinity proved to be sensitive to netilmicin. The sensitivity rate was 96% for amikacin and 97% for cefotaxime. Thirty-four patients with systemic infections and isolation of netilmicin-sensitive Enterobacteriaceae were treated with 150 mg netilmicin intravenously every 12 h. All except one patient reacted favourably. The patient who did not had a netilmicin-sensitive Escherichia coli septicaemia which recurred during treatment. The treatment was well tolerated. No ototoxicity or permanent nephrotoxicity were noted. Although the variation of serum levels was as great for netilmicin as has been reported for other aminoglycosides, they were in general within acceptable limits. In patients with reduced renal function peak levels above 16 mg/l were found five times more frequently than in patients with normal renal function. However, serum levels should also be monitored in patients with normal renal function.

Topics: Adolescent; Adult; Aged; Child; Drug Administration Schedule; Drug Resistance, Microbial; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin

Isolates of gentamicin-resistant gram-negative bacilli from clinical specimens peaked at nine to 10 per month in 1973-1974. Instituting barrier-type precautions during 1974-1977 was associated with a sustained 87% reduction in resistant Enterobacteriaceae. The number of resistant Pseudomonadaceae fell temporarily by 28%, paralleling gentamicin usage. During an endemic 15-month period in 1976-1977 nonenzymatically mediated resistant Pseudomonas aeruginosa often emerged after aminoglycoside therapy in patients who had prior carriage of sensitive strains of the same serotype (P = 0.002); this resistance was associated with wound or sputum isolates (P = 0.003). Resistant Enterobacteriaceae more often demonstrated the converse, that is, spread of urinary tract isolates with enzymatically mediated resistance from patients not on aminoglycoside therapy. These findings suggest that control measures to minimize occurrence of resistant bacilli include barrier-type precautions for patients with resistant Enterobacteriaceae, evaluation of transfers and readmissions as a source of resistant organisms, and reduction of aminoglycoside use to decrease the selection of nonenzymatic resistance.

Topics: Amikacin; Aminoglycosides; Chicago; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Gentamicins; Gram-Negative Aerobic Bacteria; Humans; Klebsiella; Microbial Sensitivity Tests; Netilmicin; Pseudomonadaceae; Pseudomonas aeruginosa; Tobramycin; Urine

30 urological patients with normal renal function were treated with netilmicin because of urinary tract infections, mostly recurrent and due to predisposing factors. the drug was given in doses of 4 mg/kg/day for 4-9 days. All but 5 patients had resolution of their signs and symptoms, and the bacteria were eliminated in 23 patients, with recurrence in 8 and reinfection in 3. The bacteria persisted in 1 patient and the results were indeterminate in 6 patients. No signs of hematopoietic, renal and hepatic toxicity occurred, and vestibular and auditory functions were undisturbed. Regular assays of serum drug concentrations revealed no signs of accumulation. Netilmicin given in doses of 4 mg/kg/day is an efficient antibiotic with low toxicity in the treatment of urinary tract infections.

Topics: Adolescent; Adult; Aged; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; 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

38 newborn infants, 28 males and 10 females, were treated with netilmicin in doses 6-7 mg/kg/day for suspected or verified infections. 19 patients were mature (mean birth weight 3169 g) and 19 were premature (mean birth weight 1864 g). 32 had moderate or severe underlying diseases. 37 babies survived, 33 were cured or improved markedly and in 4 the results were indeterminate. Pathogenic bacteria were demonstrated in 24 cases and were eliminated in 15. Only one baby died. He suffered from severe respiratory distress syndrome and Escherichia coli septicemia. No E. coli was isolated at autopsy. The mean netilmicin peak serum value was 7.7 micrograms/ml (range 1.0-30.0) and the mean trough concentration 2.1 micrograms/ml (range 0.0-9.2). No adverse effects were seen.

Topics: Bacterial Infections; Drug Evaluation; Enterobacteriaceae Infections; Female; Gentamicins; Haemophilus Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Netilmicin; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections

The efficacy and toxicity of netilmicin was assessed in 15 patients with life-threatening infections, including six with septicaemia. Fourteen patients were cured with no recurrence of infection. The initial dosage of netilmicin was 200 mg twice a day (2.3-4.0 mg/kg/dose), but subsequent adjustment of dosage was made according to the results of serum assay, either to avoid accumulation or to improve therapeutic response. Probable nephrotoxicity occurred in only one patient and there was no evidence of ototoxicity in the twelve patients who could be assessed.

Topics: Adult; Aged; Bacterial Infections; Creatinine; Drug Evaluation; Enterobacteriaceae Infections; Female; Gentamicins; Hearing; Humans; Kidney; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Staphylococcal Infections

Data obtained with 30 micrograms netilmicin discs on Mueller-Hinton agar have been compared to MIC values obtained in Mueller-Hinton broth. Regression analysis was used to determine susceptibility cutoff points for Pseudomonas and non-Pseudomonas gram-negatives. The utility of these cutoff points for the determination of netilmicin sensitivity was evaluated in tests with 1405 clinical isolates. These tests employed 897 sensitive isolates and 508 strains with known aminoglycoside resistance patterns. Netilmicin was shown to be active against sensitive isolates and those strains with resistance patterns corresponding to the presence of: ANT(2"), ANT(2")+AAC(6'), ANT(4'), APH(2")+AAC(6'), APH(3')-IV and AAC(3)-I modifying enzymes. PD50 values obtained in experimental mouse infection studies with gentamicin, tobramycin and amikacin as well as netilmicin confirmed the excellent activity of netilmicin against strains with the above-mentioned resistance patterns. The good correlation between disc sensitivity test results and MIC and PD50 values suggest that a 30 micrograms netilmicin disc can be used to predict the netilmicin susceptibility of clinical isolates.

Topics: Aminoglycosides; Animals; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Mice; Microbial Sensitivity Tests; Netilmicin; Pseudomonas; Pseudomonas Infections

An outbreak of amikacin-resistant Enterobacteriaceae (KES) occurred in the Intensive Care Nursery (ICN) of the Louisville General Hospital from January 1978 through March 1978. Epidemic disease and an increased colonization rate in newborn infants due to amikacin-resistant microorganisms has not been documented previously. Three of the 11 neonates died. The organisms isolated were resistant to amikacin and two experimental aminoglycosides, sissomicin and netilmicin. The outbreak was contained following institution of several control measures, including pharyngeal inoculation of an experimental strain of alpha streptococcus in four infants.

Topics: Amikacin; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units; Kanamycin; Klebsiella Infections; Klebsiella pneumoniae; Male; Netilmicin; Nurseries, Hospital; Serratia marcescens; Sisomicin

The in vitro efficacy of netilmicin and its synergism with penicillins were examined. Netilmicin was effective against E. coli, indole-negative and -positive Proteus, Klebsiella, Enterobacter, Salmonella, Shigella and Serratia. Netilmicin was less effective than other aminoglycosides against Citrobacter and Pseudomonas. A combination of netilmicin and piperacillin synergistically inhibited Enterococci. Netilmicin was not synergistic with either penicillin or carbenicillin against Enterococci. Netilmicin with either carbenicillin, ticarcillin or piperacillin synergistically inhibited Pseudomonas aeruginosa, but no such synergism was noted against highly resistant strains of Pseudomonas.

Topics: Amikacin; Bacteria; Drug Synergism; Enterobacteriaceae Infections; Gentamicins; Humans; Microbial Sensitivity Tests; Netilmicin; Penicillins; Pseudomonas Infections; Sisomicin; Tobramycin

Netilmicin, a new semisynthetic aminoglycoside antibiotic, was used to treat 41 infections in 38 patients. The outcome of four infections could not be evaluated: two patients received inadequate therapy and two did not have gram-negative infections. Clinical improvement occurred in 36 (97%) of the 37 gram-negative infections, and bacteriologic cure occurred in 30 (86%) of the 35 evaluable infections. Therapeutic serum concentrations of netilmicin were readily achieved by both intramuscular and intravenous routes. Reversible ototoxic effects occurred in 1 (3%) of 35 courses of therapy evaluated, reversible nephrotoxic effects occurred in 5 (14%) of 36 courses and mild reversible alterations in liver function occurred in 3 (19%) of 34 courses. Netilmicin appears to be effective and safe in the treatment of aerobic gram-negative infections.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Urinary Tract Infections

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

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.

Topics: Animals; Drug Therapy, Combination; Endocarditis, Bacterial; Enterobacteriaceae Infections; Enterococcus faecalis; Female; Netilmicin; Penicillin Resistance; Penicillins; Rabbits; Streptococcal Infections; Streptomycin

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