netilmicin and Pseudomonas-Infections

Single daily dosage of netilmicin is generally accepted in systemic infections, due to biphasic bactericidal activity and prolonged postantibiotic effect of aminoglycosides. Since little is known about the efficacy of single daily intraperitoneal application of netilmicin in the treatment of CAPD-associated peritonitis, we conducted this prospective study. Seven patients with CAPD-associated peritonitis were treated with a single daily dose of netilmicin (loading dose 1.5 mg/kg, followed by 40 mg/21 bag/day). Serum and intraperitoneal levels as well as bactericidal activity of netilmicin against Acinetobacter baumanii, E. coli and Pseudomonas aeruginosa were measured for 48 hours. Serum and peritoneal levels widely varied among the patients due to different interindividual plasma clearance of netilmicin. The intraperitoneal antibacterial action of netilmicin was decreased, more over, substantial differences in the bactericidal activity were found among the patients. However, with high initial netilmicin levels sufficient bactericidal activity was found for Acinetobacter and E. coli, but not for Pseudomonas aeruginosa. Hence, a single daily dosage of netilmicin can be a suitable treatment of CAPD-associated peritonitis, only if the dose is adapted according to the first serum and peritoneal levels. In infections with Pseudomonas aeruginosa higher peritoneal levels of netilmicin and the combination with other antibiotics will be needed for a sufficient peritoneal bactericidal activity.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

In a prospective multicenter clinical trial, 69 patients with Pseudomonas infections were treated with netilmicin sulfate as the only antipseudomonal antibiotic. Clinical resolution or improvement was observed for 81% of the infections, whereas 19% were considered treatment failures. The bacteriologic response, based on follow-up culture results, showed elimination of Pseudomonas from 62% of the infection sites, with persistence in 30%. All isolates were susceptible by disk susceptibility testing (zone greater than or equal to 15 mm), and by microdilution testing in unsupplemented broth. The majority of isolates, however, were resistant in cation supplemented media. The clinical failures could be accounted for by factors other than netilmicin failure. In conclusion, netilmicin appeared effective as treatment for netilmicin-susceptible Pseudomonas infections in nonneutropenic adults. A low incidence of nephrotoxicity (12%) occurred despite careful monitoring of serum levels.

Topics: Adult; Aged; Anti-Bacterial Agents; Drug Administration Schedule; Drug Evaluation; Drug Resistance, Microbial; Europe; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multicenter Studies as Topic; Netilmicin; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; South America; United States

High-dose anti-Pseudomonas chemotherapy is mandatory in the treatment of acute pulmonary exacerbations in patients with advanced cystic fibrosis and Pseudomonas aeruginosa isolated from their sputum. However, neither the regimen itself nor its objective evaluation have been optimized yet. In a prospective controlled evaluation 42 such exacerbations were treated for two weeks with netilmicin combined by randomisation with either azlocillin or ticarcillin. Other aspects of therapy were constant. The two therapy groups were comparable in all aspects. Both regimens produced similar improvements in clinical, radiological, laboratory, bacteriological and pulmonary function measurements. Concentrations of sputum bacteria were significantly reduced; transient eradication was documented in 29% and correlated with antibiotic susceptibility of the initially isolated Pseudomonas strains. The highly dosed antibiotics were well tolerated and emergence of resistance was rarely observed. It is concluded that both antibiotic combinations are beneficial and safe in cystic fibrosis. Monitoring of such intensive hospital treatment must include multiple parameters.

Topics: Adolescent; Adult; Azlocillin; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Drug Combinations; Female; Humans; Lung Diseases; Male; Netilmicin; Penicillins; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Function Tests; Ticarcillin

Seventeen cystic fibrosis patients aged 3.1 years to 19.8 years had 30 courses of intensive treatment for relapse of their pseudomonas chest infection. The combination of netilmicin and ticarcillin was compared with tobramycin and ticarcillin in an open study. A significant subjective and objective improvement occurred in all patients. Pseudomonas was cleared temporarily from the sputum in 11 out of the 30 courses of treatment (37%). There was no significant difference between the netilmicin and tobramycin groups, nor evidence of sustained renal or ototoxicity. Intensive therapy of pseudomonas chest infection in cystic fibrosis patients is described in detail.

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Drug Combinations; Female; Gentamicins; Humans; Lung Volume Measurements; Male; Netilmicin; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Ticarcillin; Tobramycin

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

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

In the prospective study the susceptibility of 41 Escherichia coli strains and 55 Pseudomonas aeruginosa strains to gentamicin, netilmicin and amikacin was tested at a 2-year interval (period I April 1998 to March 1999, and period II April to July 2001). Genotyping was performed by pulsed-field gel electrophoresis, and a clone based on 80% or 90% similarity was determined for each of the study bacteria. In 24 (32.0%) clones, strains showed no variation over 2-year interval, supporting the hypothesis on a priori susceptible strains. Transformation from susceptibility in period I to resistance in period II was demonstrated in 5 (6.7%) clones, a pattern consistent with the concept of bacterial development of resistance under the influence of antibiotics. However, there were 10 (13.3%) clones whose strains exhibited an inverse pattern. Accordingly, two-way transformation of susceptibility took place during the study period. The utilization of the study aminoglycosides had no major impact on the variation of microbial susceptibility. Changes in microbial susceptibility were found to follow some regular patterns, which were not influenced by the study aminoglycosides. Two phenomena were observed: (i) there were stable clones that did not develop resistance in spite of selective antibiotic challenge; and (ii) changes of susceptibility in isolated bacteria from both inpatient and outpatient strains of the same clone were two-way and reversible.

Topics: Amikacin; Aminoglycosides; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Genotype; Gentamicins; Humans; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections

Intubated patients frequently become colonized by Pseudomonas aeruginosa, which is subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires resistance against available antimicrobials. Depending on the resistance mechanism selected for, resistance might either be lost or persist after removal of the selective pressure. We investigated the rapidity of selection, as well as the persistence, of antimicrobial resistance and determined the underlying mechanisms. We selected 109 prospectively collected P. aeruginosa tracheal isolates from two patients based on their prolonged intubation and colonization periods, during which they had received carbapenem, fluoroquinolone (FQ), or combined beta-lactam-aminoglycoside therapies. We determined antimicrobial resistance phenotypes by susceptibility testing and used quantitative real-time PCR to measure the expression of resistance determinants. Within 10 days after the initiation of therapy, all treatment regimens selected resistant isolates. Resistance to beta-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined beta-lactam-aminoglycoside resistance was associated with the appearance of small-colony variants. Imipenem and FQ resistance persisted for prolonged times once the selecting antimicrobial treatment had been discontinued. In contrast, resistance to beta-lactams disappeared rapidly after removal of the selective pressure, to reappear promptly upon renewed exposure. Our results suggest that resistant P. aeruginosa is selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to the loss or persistence of resistance after the removal of the selecting agent. Even if resistant isolates are not evident upon culture, they may persist in the lung and can be rapidly reselected.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Resistance, Bacterial; Humans; Longitudinal Studies; Pneumonia, Ventilator-Associated; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections

In this study, we systematically investigated the resistance mechanisms to beta-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary beta-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactams; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Fluoroquinolones; Genotype; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction

We report the results of a microbiological clinic study that was performed by our ENT Department between years 2000 and 2001 whose main objective was to determine, in Badajoz Area of Health, which bacteria were involved in the acute diffuse external otitis of patients without previous antibiotic treatment (two weeks before obtaining the samples). Of 79 isolated microorganisms in 62 patients that fulfilled the requirements established Pseudomonas, mainly P. Aeruginosa, represented a 46.83% altogether followed by Staphylococcus (18.98%). In almost one fourth part of the cases strains of associated fungi were identified.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Age Factors; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Ciprofloxacin; Data Interpretation, Statistical; Female; Fungi; Humans; Male; Middle Aged; Mycoses; Netilmicin; Otitis Externa; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Sex Factors; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Treatment Outcome

Peritonitis due to Pseudomonas species is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. The clinical course of peritonitis due to Pseudomonas complicating CAPD remains unclear.. All of the Pseudomonas species episodes of peritonitis in our dialysis unit were studied from 1995 to 1999. During this period, there were 859 episodes of peritonitis recorded, 113 of which were caused by the Pseudomonas species. Nine episodes were excluded because they were mixed growth. The remaining 104 episodes in 68 patients were reviewed.. The underlying renal diagnosis and prevalence of comorbid conditions of the 68 patients were similar to those found in our entire dialysis population. There was a history of antibiotic therapy within 30 days of the onset of peritonitis due to the Pseudomonas species in 69 episodes (66.3%). In 47 episodes (45.2%) there was a concomitant exit site infection. The overall primary response rate was 60.6% and the complete cure rate was 22.1%. The presence of exit site infection was associated with a lower primary response rate (22 in 47 vs. 41 in 57 episodes, P < 0.01) and a lower complete cure rate (5 in 47 vs. 18 in 57 episodes, P < 0.02). The episodes that had received recent antibiotic therapy had a significantly lower complete cure rate than the de novo cases (8 in 69 vs. 15 in 35 episodes, P < 0.001). Episodes receiving third-generation cephalosporin as part of the initial antibiotic regimen had a significantly higher primary response rate than the ones that initially received aminoglycoside (54 in 81 episodes vs. 8 in 22 episodes, P < 0.05), but their complete cure rates were similar. Twenty-four cases failed to respond to antibiotics and the Tenckhoff catheter was removed. The chance of returning to CAPD was higher when the Tenckhoff catheter was removed on day 10 than on day 15 (9 in 14 cases vs. 5 in 10 cases), although the result was not statistically significant. The Tenckhoff catheter was removed and replaced at another site simultaneously in another 14 cases after the effluent cleared up. None of these patients had a relapse of peritonitis within three months.. Recent antibiotic therapy is the major risk factor for peritonitis due to the Pseudomonas species. Exit site infection and recent antibiotic therapy are associated with poor therapeutic response to antibiotics. When the therapeutic response is suboptimal, early Tenckhoff catheter removal may help preserve the peritoneum for further peritoneal dialysis. Elective Tenckhoff catheter exchange after clearing up the peritoneal dialysis effluent may also reduce the likelihood of relapse. It is desirable to use third-generation cephalosporin in the initial antibiotic regimen for peritonitis treatment in localities with a high incidence of peritonitis due to the Pseudomonas species.

Topics: Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Equipment Contamination; Female; Gentamicins; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Pseudomonas Infections; Retrospective Studies; Secondary Prevention; Vancomycin

Different methods have been described for determination of the post-antibiotic effects (PAEs) of antibiotics, from the conventional methods to the automatic measurement of bacterial regrowth. The PAEs of ciprofloxacin, ofloxacin and perfloxacin, as compared with those of amikacin, netilmicin and ceftazidime, have now been investigated for three clinical isolates of Pseudomonas species, using automated measurement of the growth with an Anthos microplate reader. It was found that, besides the well-known PAEs of aminoglycosides, quinolone antibiotics also exhibit drug- and concentration-dependent PAEs against clinical isolates of Pseudomonas when used in concentrations of 1/2x, 1 x or 5 x MIC. Of the three quinolones tested, pefloxacin showed the greatest PAE, independently of its MICs against the different strains. Ofloxacin had no or only an insignificant PAE, while ciprofloxacin had a marked PAE for all strains, including the reference strains.

Topics: 4-Quinolones; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Automation; Ceftazidime; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Netilmicin; Ofloxacin; Pefloxacin; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections

Imipenem (CAS 64221-86-9) as well as netilmicin (CAS 56391-57-2) at suprainhibitory concentrations induced the postantibiotic effects against three P. aeruginosa strains. Imipenem (2 x or 4 x minimal inhibitory concentration (MIC)) showed postantibiotic effects in the range of 0.3-1.6 h and 0.9-4.0 h. Netilmicin at the same concentrations produced postantibiotic effects of 3.0-3.8 h and 3.5-4.5 h. Postantibiotic effects manifested by imipenem (2 x or 4 x MIC) + netilmicin (2 x MIC) combination were somewhat longer (in the range of 4.6-4.9 h and 5.8-7.4 h) than the mathematical sum of postantibiotic effects induced by drugs alone (in the range of 4.1-4.7 h and 4.7-7.0 h).

Topics: Carbapenems; Drug Therapy, Combination; Gentamicins; Humans; Imipenem; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

The postantibiotic effect (PAE) (postantibiotic phase induced by 2x or 4x MIC) as well as the postantibiotic effect of subinhibitory concentrations (0.1x, 0.2x and 0.3x MIC) (PA SME) of netilmicin, tobramycin, ciprofloxacin and pefloxacin affected the production of the virulence factor alginate by a P. aeruginosa strain. Aminoglycosides and ciprofloxacin at a concentration of 4x MIC inhibited the alginate production more significantly than 2x MIC. Suprainhibitory concentrations of aminoglycosides were more effective than pefloxacin (2x or 4x MIC) and ciprofloxacin (2x MIC). PA SME demonstrated by the above antibiotics (with the exception of ciprofloxacin 2x MIC + 0.1x MIC) suppressed alginate production more efficiently.

Topics: Alginates; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Cross Infection; Depression, Chemical; Dose-Response Relationship, Drug; Gentamicins; Glucuronic Acid; Hexuronic Acids; Humans; Microbial Sensitivity Tests; Netilmicin; Pefloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Virulence

The antipseudomonal activities of ceftriaxone (CEF) or ceftazidime (CAZ), each combined with tobramycin (TOB) or netilmicin (NET), against 90 clinically significant Pseudomonas aeruginosa isolates were examined both by checkerboard and time-kill assays. As expected, susceptibility testing of single antibiotics by agar dilution demonstrated good activity for CAZ (89% susceptible), TOB (94%), and NET (58%), but poor activity for CEF (15%). Checkerboard studies revealed striking synergy (FIC indices < or = 0.5) for CEF, however, in combination with either TOB (72%) or NET (81%), compared with CAZ-TOB (44%) or CAZ-NET (60%) (P < 0.01, respectively). No antagonism (FIC indices > or = 4) was found in any of these combinations. The MIC90s of CEF, CAZ, or aminoglycosides in the combinations were reduced at least fourfold: CEF, from > 128 to 32 mg/liter; CAZ, from 16 to 4 mg/liter; TOB, from 4 to 0.5 mg/liter; and NET, from 32 to 4 mg/liter. With CEF and NET, the percentage of strains sensitive to < or = 8 mg/liter of both drugs alone and in combination increased from 9% to 69%. Results of the time-kill assay for CEF-NET agreed reasonably well with the checkerboard method (Spearman rank correlation coefficient, 0.40, P < or = 0.01), and generated a bactericidal outcome in 60% (24 of the 40 isolates), when tested with combinations at 1/4 MBC of either antibiotic alone. Importantly, concentrations of CEF and aminoglycoside combinations that demonstrated synergy by either checkerboard or time-kill assays were achievable in serum clinically. These data suggest a unique interaction of CEF-aminoglycoside combinations against P. aeruginosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ceftazidime; Ceftriaxone; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The bactericidal activities of arbekacin (ABK), vancomycin (VCM), gentamicin (GM) and netilmicin (NTL) in mixed culture with Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were examined using an in vitro computer programmed pharmacokinetic simulation system and also the protective effect of these agents on systemic infection in neutropenic mice was examined. In a mixed culture of S. aureus No. 235 (MRSA) and P. aeruginosa E7, ABK showed a strong bactericidal activity and an inhibition of regrowth against both bacteria, and GM and NTL showed similar effects. On the other hand, VCM showed a bactericidal activity against S. aureus No. 235, but not against P. aeruginosa. In the protective study, ABK was evidently more effective than GM, NTL or VCM against a systemic mixed infection of mice with S. aureus No. 235 and P. aeruginosa E7. In brief, the ED50 values of ABK, VCM, GM and NTL were 19.5, > 100, 40.5 and 45.2 mg/kg, respectively.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Computer Simulation; Dibekacin; Gentamicins; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

A 53-year-old woman was admitted because of a two weeks' history of progressive perineal pain, low-grade fever, a high erythrocyte sedimentation rate, and tenderness over the inferior rami of the pubic bone. Osteomyelitis was suspected. However, bone scanning, computed tomography, and magnetic resonance imaging of the pelvis showed no evidence of intraosseous disease, but revealed signs of inflammation in the surrounding soft tissue. Conventional antimicrobial therapy was unsuccessful. Biopsy of the bone demonstrated active osteomyelitis and the cultures grew Pseudomonas aeruginosa. Osteomyelitis of the pubic bone and symphysis is most often a sequel to pelvic surgery but has also been observed in i.v. drug abusers. In both circumstances Pseudomonas aeruginosa has frequently been identified as the causative agent. Pelvic osteomyelitis is extremely rare in patients without predisposing factors. Osteomyelitis can only be differentiated from osteitis pubis, a non-infectious inflammatory disease, by bone biopsy. The treatment of choice for osteomyelitis is a beta-lactam antibiotic effective against pseudomonas in combination with an aminoglycoside for 4-6 weeks. Recent studies have demonstrated that new generation quinolones are also effective.

Topics: Ceftazidime; Drug Therapy, Combination; Female; Humans; Middle Aged; Netilmicin; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Pubic Bone; Radiography

Noma has virtually disappeared from Europe, but is still found in certain parts of Africa, South America and Asia. In our case the etiologic agent was Pseudomonas aeruginosa sensitive to antibiotic therapy that we used (pefloxacin and netilmicin). Another characteristic aspect of our case is the rapid infaust evolution. In this report will be discuss the pathogenesis and the reason of the failure of the antibiotic therapy especially in immunodeficiency patients.

Topics: 4-Quinolones; Acute Disease; Adult; Anti-Infective Agents; Drug Hypersensitivity; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Leukemia, Myeloid; Netilmicin; Noma; Pefloxacin; Penicillins; Pseudomonas Infections; Quinolones

The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation.

Topics: Animals; Male; Mice; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Conventional Syrian hamsters, contaminated with Giardia spp., Spironucleus muris, Trichomonas spp., Pasteurella pneumotropica and Pseudomonas aeruginosa were treated with chemicals in order to obtain specific pathogen free animals. Hamsters kept in the laminar flow rack were treated orally with metronidazole several times to obtain a flagellate-free colony. After all flagellates had been eradicated, one pair of animals were kept in an isolator and mating was allowed to occur. When their offspring reached the age of seven weeks, they were intramuscularly injected daily with netilmicin sulfate for 10 consecutive days. Following these treatments, all of the hamsters were free of Pasteurella and Pseudomonas. Further breeding of these animals was continued in isolators. To confirm the absence of selected pathogens, they were placed in a barrier room for further breeding as specific pathogen free animals.

Topics: Animals; Breeding; Cricetinae; Female; Male; Mesocricetus; Metronidazole; Netilmicin; Pasteurella Infections; Protozoan Infections; Pseudomonas Infections; Specific Pathogen-Free Organisms

The first exposure of gram-negative bacilli to an aminoglycoside antibiotic in vitro induces a biphasic bactericidal response and adaptive drug resistance (G. L. Daikos, G. G. Jackson, V. T. Lolans, and D. M. Livermore, J. Infect. Dis. 162:414-420, 1990; G. G. Jackson, G. L. Daikos, and V. T. Lolans, J. Infect. Dis. 162:408-413, 1990). The therapeutic implications were examined in netilmicin treatment of a Pseudomonas aeruginosa infection of normal and neutropenic mice. For 2 h after the first dose, the bactericidal rates were rapid, 0.75, 1.0, and 1.5 log10 CFU/h with doses of 10, 30, and 60 mg/kg, respectively. Each twofold increase in dosage reduced the number of surviving bacteria fivefold. Between 2 and 6 h, the second-phase bactericidal rate was slow, less than or equal to 0.3 log10 CFU/h, regardless of the dose. In a multiple-dose regimen, the same amount of netilmicin given in one dose was 70 and 90% more effective than two or three doses, respectively. Doses calculated to keep the drug level in plasma above the MIC were less effective than regimens giving first exposure to a high drug concentration. Adaptive resistance occurred when doses were given more than 2 h after the start of treatment. Temporary survival of bacteremic neutropenic mice was 60 to 70% greater with a second dose at 2 h than after a longer interval. In a thigh infection of neutropenic mice treated every 2 h, doses 4, 6, and 8 h after the first one showed no bactericidal effect. A drug-free interval of 8 h (20 times the drug half-life) renewed bacterial susceptibility to drug action. The results in vivo confirm the biphasic bactericidal action and induction of adaptive resistance that characterized first exposure of gram-negative bacilli to aminoglycoside antibiotics. The phenomena have meaning for the optimum clinical use of aminoglycosides.

Topics: Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Microbial; Female; Mice; Mice, Inbred ICR; Netilmicin; Pseudomonas Infections; Time Factors

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a beta-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.

Topics: Animals; Anti-Bacterial Agents; Ceftazidime; Colony Count, Microbial; Colony-Stimulating Factors; Cyclophosphamide; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Leukocyte Count; Male; Mice; Mice, Inbred ICR; Muscles; Muscular Diseases; Netilmicin; Neutrophils; Pseudomonas Infections

We studied the intestinal flora of 23 newborns, whose meconium had yielded a pure culture of Pseudomonas aeruginosa on blood agar medium. Twelve infants had a single serotype of P. aeruginosa in their meconium, 10 had a second serotype and the last infant was carrying three distinct ones. The maximum levels of P. aeruginosa observed during the first week of life were variable among the infants: 1 x 10(3) to 1 x 10(10) CFU/g of stools. The levels diminished progressively afterwards, and after 1 year of age only 1 of the 13 infants examined remained a carrier of P. aeruginosa. In 11 infants a second or a third serotype occurred during the course of the study. The serotypes that appeared secondarily always disappeared before the initial ones. Antibiotics: ampicillin + gentamicin or cefotaxime + netilmicin and colistin which were given to 8 infants had no clear effect on P. aeruginosa levels. Four infants had delayed colonization by Escherichia coli of greater than or equal to 10 days. All 4 had high levels of P. aeruginosa: 1 x 10(7) to 1 x 10(10) CFU/g stool, and antibiotic therapy, rendering it impossible to assess which was the cause of this delay. This colonization by P. aeruginosa did not lead to any clinical trouble.

Topics: Cefotaxime; Colistin; Drug Therapy, Combination; Escherichia coli; Feces; Female; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Intestinal Diseases; Male; Meconium; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping; Ticarcillin; Time Factors

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

Topics: Ciprofloxacin; Drug Therapy, Combination; Female; Humans; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Pseudomonas Infections

A granulocytopenic mouse model was used to elucidate the impact of dose spacing on the activity of netilmicin against Pseudomonas aeruginosa. A thigh infection was produced and then treated with netilmicin combined with azlocillin. Netilmicin was injected subcutaneously at decreasing doses every 20 min to result in plasma-concentration-time curves similar to those observed in patients on intravenous netilmicin treatment. A once-daily regimen was simulated and compared to a simulated conventional schedule of every 8 h. Identical total amounts of drug were used in both groups of comparatively treated mice. Therapeutic efficacy was quantitated by repeated determinations of surviving organisms in thigh homogenates. Combination therapy was significantly more effective than azlocillin treatment alone. In combination regimens the simulated once-daily netilmicin schedule killed the target organisms faster than the simulated thrice-daily regimen and was significantly more efficacious by 24 and 32 h in two out of three strains of Pseudomonas aeruginosa tested. It is concluded that the results of combination therapy of severe Pseudomonas aeruginosa infections in the immunocompromised host might be improved by choosing an aminoglycoside dosage interval of 24 h instead of the conventional 8 h.

Topics: Animals; Azlocillin; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Mice; Netilmicin; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.

Topics: Abscess; Animals; Anti-Infective Agents; Aortic Valve; Azlocillin; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Kidney Diseases; Microbial Sensitivity Tests; Netilmicin; Penicillin Resistance; Pseudomonas Infections; Quinolines; Rabbits

In artificial pseudomonas infections undertaken on white mice the effectiveness of the aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) was compared. The most effective drugs on highly susceptible Ps. aeruginosa were amikacin and netilmicin. Moreover amikacin is probably capable of inhibiting pseudomonas toxin production. Therefore this preparation should be left in reserve for the treatment of serious pseudomonas processes.

Topics: Amikacin; Aminoglycosides; Animals; Mice; Mice, Inbred Strains; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections

Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, alpha 1-proteinase inhibitor (alpha 1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and alpha 1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of alpha 1-PI and BMI increased significantly (P less than .05), a high level of free GE persisted. No active alpha 1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P less than .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of alpha 1-PI, both compounds currently produced by recombinant DNA technology.

Topics: alpha 1-Antitrypsin; Anti-Bacterial Agents; Azlocillin; Blood Proteins; Bronchi; Cystic Fibrosis; Granulocytes; Humans; Netilmicin; Pancreatic Elastase; Protease Inhibitors; Proteins; Pseudomonas Infections; Serpins; Sputum; Ticarcillin

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Female; Gentamicins; Humans; Metabolic Clearance Rate; Mice; Netilmicin; Peritonitis; Pseudomonas Infections; Ticarcillin

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

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

The efficacy of various dosage schedules of netilmicin against Pseudomonas aeruginosa has been compared using an in vivo model (normal and granulocytopenic mice). Bolus injections were at least as effective as simulated short infusions or simulated continuous infusions of identical total amounts of netilmicin.

Topics: Agranulocytosis; Animals; Delayed-Action Preparations; Disease Models, Animal; Gentamicins; Infusions, Parenteral; Injections, Intravenous; Mice; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections

Netilmicin was intramuscularly injected at a daily dose of 200 mg, divided twice, for 5 to 10 days to 14 patients with complicated urinary tract infection caused by P. aeruginosa. The clinical results were excellent in 7 cases, good in 5 cases, and fair in 2 cases. Neither side effects nor abnormal values in laboratory findings were reported. The MIC of netilmicin against 14 strains of P. aeruginosa isolated from the above patients were distributed between 3.13 micrograms/ml and 12.5 micrograms/ml except 1 strain at inoculum size 10(6) cells/ml.

Topics: Aged; Drug Evaluation; Drug Resistance, Microbial; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

Patients with exacerbations of chronic urinary tract infection due to Pseudomonas aeruginosa were treated for 10 days with either ceftazidime or netilmicin. Bacteriuria was eliminated in all 15 patients who received ceftazidime but recurred in 11. Of 13 patients treated with netilmicin, pseudomonas was eradicated in eight but recurred in six.

Topics: Adult; Aged; Anti-Bacterial Agents; Blood Cell Count; Blood Chemical Analysis; Ceftazidime; Female; Humans; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Urinary Tract Infections

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

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

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

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.

Topics: Bacterial Infections; Escherichia coli Infections; Gentamicins; Humans; Injections, Intravenous; Klebsiella Infections; Neoplasms; Netilmicin; Pseudomonas Infections

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

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