netilmicin and Escherichia-coli-Infections

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.. A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).. Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).. The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract 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

A prospective, randomised trial was undertaken to compare the efficacy of ciprofloxacin and netilmicin for the treatment of acute pyelonephritis. Forty-three patients were enrolled and 34 (29 women) completed the protocol. Fifteen of 17 patients treated with ciprofloxacin and 15 of 17 treated with netilmicin were cured. All patients were treated for five days. One patient relapsed after ciprofloxacin and another had a reinfection, while two relapsed after netilmicin. Five of six patients with a urinary tract abnormality were cured. Side effects were generally mild and rapidly reversible. Patients treated with ciprofloxacin spent a mean of 3.7 days in hospital compared with 5.3 days for those treated with netilmicin. The difference in duration of hospital stay was statistically significant (p less than 0.01). Both drugs proved highly effective and safe for the treatment of severe acute pyelonephritis.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Ciprofloxacin; Escherichia coli Infections; Female; Hospitalization; Humans; Infusions, Intravenous; Injections, Intravenous; Length of Stay; Male; Middle Aged; Netilmicin; Prospective Studies; Pyelonephritis; Recurrence

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: Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant; Male; Netilmicin; Random Allocation; Urinary Tract Infections

Women with uncomplicated urinary tract infections were randomly allocated to either a single 150 mg intramuscular dose of netilmicin or a standard five-day course of oral co-trimoxazole. Twenty-one of 22 were cured with netilmicin and all 20 with co-trimoxazole. No patient treated with netilmicin developed any side effects or obvious toxicity. Following co-trimoxazole one woman developed a severe skin rash and another nausea. Netilmicin is another drug which is highly effective when used in a single dose regimen for the treatment of uncomplicated urinary tract infections. There are many advantages of this approach to the management of a common clinical problem.

Topics: Administration, Oral; Adolescent; Adult; Clinical Trials as Topic; Drug Combinations; Escherichia coli Infections; Female; Gentamicins; Humans; Injections, Intramuscular; Middle Aged; Netilmicin; Prospective Studies; Random Allocation; Staphylococcal Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Thirty children with serious gram-negative infections were treated with either netilmicin, 2 mg/kg, or tobramycin, 1 mg/kg, every eight hours for a minimum of 72 hours. Because of the administration of different doses, a "blind" investigator evaluated treatment response while another investigator adjusted the doses on the basis of each patient's drug serum levels and bacteriological response. Comparisons between the two study groups showed both treatments to be equally effective. All 15 patients treated with netilmicin and 14 of the 15 patients treated with tobramycin experienced complete resolution of clinical signs and symptoms and elimination of pathogens. One child in the tobramycin group was considered a treatment failure because of a persistent urinary tract infection. There were no adverse effects attributable to either drug.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Netilmicin; Respiratory Tract Infections; Tobramycin; Urinary Tract Infections

Escherchia coli isolated, from urine samples were studied for their antibiotic susceptibility patterns, with special reference to the new antimicrobial compound fosfomycin and their correlation with various virulence factors.. The mid stream urine samples received in the department were processed and identification was done by using the standard culture and identification techniques. The antibiotic susceptibility testing was done by modified Kirby-Bauer disk diffusion and the disk diffusion method was used to confirm the ESBL, AmpC, MBL production by the UPEC. Various virulence factors like hemolysin, haemagglutinaton, gelatinase, siderophore production, biofilm formation, serum resistance and hydrophobicity were detected.. Fosfomycin was found to be most effective agent (100%) against uropathogenic E.coli followed by netilmicin (89.5%). The least effective agents were ampiciilin and cotrimoxazole. Twenty nine percent (29%) isolates were found to be multi drug resistant (MDR).. The testing of the newer therapeutic agents like fosfomycin will add on to therapeutics for UTI's.

Topics: Ampicillin; Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Netilmicin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Urine; Uropathogenic Escherichia coli; Virulence Factors

Escherichia coli is considered as the most common cause of urinary tract infection (UTI) and acquired multiple resistances to a wide range of antibiotics such as aminoglycosides. Enzymatic alteration of aminoglycosides (AMEs) by aminoglycoside- modifying enzymes is the main mechanism of resistance to these antibiotics in E. coli. The aim of this study was detection and investigation of frequency of genes encoding aminoglycoside modifying enzymes (aac(3)-IIa and ant(2'')-Ia) in UPEC isolated from hospitalized patients in teaching hospital of Tehran, Iran.. A total of 276 UPEC were obtained from Urine samples in a hospital from Tehran. Antibiotic susceptibility to aminoglycosides was determined by disk diffusion method according CLSI guidelines in UPEC isolates. MICs of target antibiotics were determined by agar dilution method. All isolates were screened for the presence of the AMEs genes using the PCR. The results of disk diffusion showed 21%, 24.6%, 23.18%, 3.62% and 6.15% of isolates were resistant to Gentamicin, Tobramycin, Kanamicin, Amikacin and Netilmicin respectively. The agar dilution's results (MICs) were high, 66.19% for Gentamicin. The aac (3)-IIa and ant(2″)-Ia genes were detected in (78.87%) and 47.88% of isolates respectively.. This study shows the high frequency of genes encoding (AMEs) aac(3)-IIa and ant(2")-Ia genes and their relationship between different aminoglycoside resistance phenotypes.

Topics: Amikacin; Anti-Bacterial Agents; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Escherichia coli Infections; Gene Expression Regulation, Bacterial; Gene Frequency; Genes, Bacterial; Gentamicins; Hospitals, Teaching; Humans; Iran; Kanamycin; Netilmicin; Tobramycin; Urinary Tract Infections; Uropathogenic Escherichia coli

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

One hundred twenty-one extended-spectrum beta-lactamse-producing enterobacterial clinical isolates were screened for the qepA gene. A single CTX-M-15-positive Escherichia coli isolate (0.8%) that produced the putative pump QepA2 was identified. This qepA2 gene was located onto a 90-kb mobilizable plasmid that conferred reduced susceptibility to hydrophilic fluoroquinolones.

Topics: Aged; Base Sequence; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fluoroquinolones; France; Genes, Bacterial; Humans; Models, Genetic; Molecular Sequence Data; Plasmids

The prevalence of antimicrobial resistance among uropathogenic E. coli varies widely worldwide; to guide empirical therapy is necessary to have local, up-to-date susceptibility data.. We tested 907 isolates from patients in Mexico City by disk diffusion and further characterized ciprofloxacin, cephalosporin and nitrofurantoin resistant strains.. Isolates were mostly resistant to ampicillin (74%), trimethoprim-sulfamethoxazole (60.1%) and ciprofloxacin (32.6%). The most effective drug was netilmicin (5.1% resistant) and the most effective of oral drugs was nitrofurantoin (7.4% resistant). Sixty-percent of ciprofloxacin-resistant strains had minimal inhibitory concentrations of 125 microg/ml or higher, well beyond urinary concentrations at the end of the 12-hour inter-dose period for standard oral regimes. Extended-spectrum beta-lactamases were detected in 6% of strains, most of them from community-acquired infections. All strains resistant to nitrofurantoin carried a 20 Kb plasmid, which when transformed into a susceptible recipient, conferred resistance to nitrofurantoin, ampicillin, sulfonamides, streptomycin, and partially protected against ciprofloxacin.. Drugs considered of choice against uncomplicated urinary tract infections are facing high resistance prevalences and resistance determinants formerly seen only at hospitals are now among community strains. Treatment guidelines from developed countries might not reflect these local trends.

Topics: Ampicillin; Anti-Bacterial Agents; Ciprofloxacin; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Humans; Mexico; Microbial Sensitivity Tests; Netilmicin; Nitrofurantoin; Pregnancy; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Uropathogenic Escherichia coli

Escherichia coli is a leading cause of bacteraemia. The aim of this study was to evaluate all E. coli positive blood cultures collected during a 4-y period in a haematological department using piperacillin plus netilmicin for empiric treatment of febrile episodes. We measured the incidence of piperacillin-resistant E. coli bacteraemia among haematological and non-haematological patients, described the importance of previous antibiotic treatment for resistance development in E. coli and evaluated the impact of piperacillin resistance on the clinical outcome of E. coli bacteraemia. 114 episodes of E. coli bacteraemia in 104 patients were recorded and 98 episodes in 88 patients (42 males and 46 females) with a median age of 64 y (range 19-85 y) were evaluated. In 81.6% of the episodes the patients had a haematological disorder, dominated by acute leukaemia (41.3%), chronic leukaemia (16.3%) and lymphoma (10%). The proportion of piperacillin-resistant E. coli was higher among haematological patients than non-haematological patients (25% vs 0%, p=0.02) and resistance was associated with piperacillin therapy during the previous month (p=0.05). No difference in clinical outcome was found between haematological patients infected with piperacillin-susceptible or -resistant E. coli (intensive care 12% vs 15%; mortality 22% vs 25%).

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Denmark; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Humans; Incidence; Male; Medical Records; Middle Aged; Netilmicin; Piperacillin; Retrospective Studies

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

A case of retroperitoneal pulmonary fistula caused by a neonatal adrenal abscess is reported. The adrenal abscess was diagnosed by means of needle aspiration which guided the choice of antibiotic therapy. The fistula was demonstrated by direct injection of contrast medium into the adrenal abscess. Treatment by needle aspiration of the adrenal abscess and intravenous antibiotics was successful.

Topics: Abscess; Adrenal Gland Diseases; Anti-Bacterial Agents; Bronchial Fistula; Cefotaxime; Cephalosporins; Contrast Media; Escherichia coli Infections; Fistula; Gentamicins; Humans; Infant, Newborn; Injections, Intravenous; Lung Diseases; Male; Needles; Netilmicin; Suction; Tomography, X-Ray Computed

One-hundred women suffering from acute pyelonephritis were hospitalized for less than 4 days on average, in order to make a diagnosis based on bacteriology and computerized tomography (CT) and to bring fever down with a 21-day antibiotic therapy. In cases of acute pyelonephritis due to a urinary tract obstacle, endoscopic uereteral drainage was added to the antibiotic treatment. In the absence of obstacle, medical treatment was sufficient to obtain apyrexia. Fluoroquinolone therapy made it possible to reduce the hospital stay to 2 or 3 days, depending on whether the lesions observed at CT were triangular or round.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Ampicillin Resistance; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Length of Stay; Middle Aged; Netilmicin; Pefloxacin; Pyelonephritis; Urography

The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated. Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with ciprofloxacin-treated E. coli was significantly lower than that of mice immunized with E. coli untreated or treated with other antibiotics. Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains. The better protection observed in mice immunized with ciprofloxacin-treated E. coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.

Topics: Animals; Anti-Bacterial Agents; Aztreonam; Blood Bactericidal Activity; Ceftriaxone; Ciprofloxacin; Complement System Proteins; Enzyme-Linked Immunosorbent Assay; Epitopes; Escherichia coli; Escherichia coli Infections; Female; Immunization; Immunoglobulin G; Immunoglobulin M; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Netilmicin; Opsonin Proteins; Phagocytosis

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Topics: Animals; beta-Lactamase Inhibitors; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Microbial Sensitivity Tests; Netilmicin; Rabbits; Sulbactam

The role of serum levels on the intrarenal accumulation kinetics of gentamicin and netilmicin in normal and infected kidneys was evaluated in a short-term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin and netilmicin achieving individual steady-state serum levels ranging from 0.5 to 120 micrograms/ml. The model of pyelonephritis used resulted in severe left pyelonephritis and mild right pyelonephritis. Only the right infected kidneys were studied. Gentamicin and netilmicin cortical concentrations were analysed as a function of serum levels by linear (least-squares regression analysis) and non-linear regression. For the non-linear regression analysis, the Michaelis-Menten kinetic was the best fitting curve. Steady-state elevation of serum concentrations of gentamicin and netilmicin was associated with a non-linear increase of cortical concentrations in normal kidneys, suggesting a saturable process. By contrast, in the mildly-infected right kidneys, the steady-state elevation of serum concentrations of gentamicin was associated with a linear increase of cortical concentrations while the accumulation kinetic of netilmicin showed a saturable process. At lower serum levels (therapeutic range, from 0.5 to 15 micrograms/ml) both gentamicin and netilmicin showed a first order kinetics of accumulation and netilmicin accumulated less than gentamicin in normal kidneys (p = 0.0004). By contrast, the uptake of netilmicin was higher in the right infected kidneys, as compared to the uptake of netilmicin in the normal kidneys, (p = 0.00005), and as compared to gentamicin in the respective kidneys. We conclude that renal infection modifies the intrarenal accumulation of aminoglycosides.

Topics: Animals; Creatinine; Escherichia coli Infections; Female; Gentamicins; Kidney Cortex; Kinetics; Metabolic Clearance Rate; Netilmicin; Pyelonephritis; Rats; Rats, Inbred Strains

The effect of sub-MICs of netilmicin and ceftriaxone on the interaction between encapsulated and unencapsulated strains of Escherichia coli and certain host defence mechanisms, i.e. complement activation, opsonization, phagocytosis by human polymorphonuclear leucocytes (PMN), and serum bactericidal activity have been studied. Experiments were carried out testing antibiotics either alone or in combination. Non-capsulated strains of E. coli activated complement rapidly and were easily phagocytosed and killed after opsonization in human pooled serum. Pretreatment of these strains with sub-MICs of antibiotics did not change the rate of opsonization or the degree of uptake by PMN, but did enhance serum sensitivity. Capsulated strains of E. coli were both poorly opsonized and resistant to serum bactericidal activity. Treatment of these strains with sub-MICs of antibiotics enhanced complement consumption as well as phagocytosis by PMN, but did not affect serum-resistance.

Topics: Blood Bactericidal Activity; Ceftriaxone; Complement System Proteins; Escherichia coli; Escherichia coli Infections; Hemolytic Plaque Technique; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Netilmicin; Neutrophils; Opsonin Proteins; Phagocytosis

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

Topics: Animals; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli Infections; Female; Half-Life; Humans; Male; Netilmicin; Rabbits

Treatment efficacy with netilmicin sulphate/methylprednisolone sodium succinate in a severe septic shock baboon model, using an LD100 of live Escherichia coli, was evaluated. All the animals treated with both netilmicin and methylprednisolone were permanent (greater than or equal to 7 days) survivors, whereas none of the untreated baboons lived more than 24 hours. These results indicate that, in a baboon model, netilmicin is an effective alternative to gentamicin (with methylprednisolone) in the treatment of severe septic shock.

Topics: Animals; Drug Therapy, Combination; Escherichia coli Infections; Female; Male; Methylprednisolone; Netilmicin; Papio; Shock, Septic

Topics: Acute Disease; Bacterial Infections; Child; Child, Preschool; Dysentery, Bacillary; Enteritis; Escherichia coli Infections; Female; Gentamicins; Humans; Infant; Male; Netilmicin; Salmonella Infections

Dogs permanently recover (survive at least seven days) from lethal doses of Escherichia coli when treated early with intravenous (IV) intermittent infusions of methylprednisolone sodium succinate and gentamicin sulfate. We evaluated the therapeutic effectiveness of constant or bolus IV infusion of methylprednisolone combined with gentamicin or netilmicin sulfate. Four groups of anesthetized dogs were infused for one hour with E coli and treated as follows (% survival indicated): no treatment (0%); constant infusion of methylprednisolone and gentamicin (100%); bolus infusion of methylprednisolone and gentamicin (57%); and constant infusion of methylprednisolone and netilmicin (83%). Constant or bolus infusion of methylprednisolone was begun 15 minutes after E coli infusion was started. Gentamicin or netilmicin administration was begun when all organisms had been infused. The probability of recovery from shock was significantly increased when dogs were treated with constant infusion of methylprednisolone and intermittent infusions of gentamicin or netilmicin, but was only moderately increased when treated with intermittent bolus infusions of methylprednisolone and intermittent infusions of gentamicin.

Topics: Animals; Blood Pressure; Dogs; Drug Evaluation; Drug Therapy, Combination; Escherichia coli Infections; Female; Gentamicins; Heart Rate; Infusions, Parenteral; Male; Methylprednisolone; Methylprednisolone Hemisuccinate; Netilmicin; Shock, Septic; Time Factors

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

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 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