netilmicin and Gram-Positive-Bacterial-Infections

This study compares the clinical and microbiologic value of topical netilmicin with that of gentamicin in the treatment of acute bacterial conjunctivitis.. A double-blind, randomized, prospective, controlled study was performed in 209 patients. One to two drop(s) of either antibiotic was applied to the affected eye(s) four times a day for up to 10 days. Patients were examined at the time of diagnosis and after 3, 5, and 10 days. Clinical efficacy was measured as the cumulative sum score (CSS) of the key signs and symptoms of acute bacterial ocular infection. Sensitivity/resistance was evaluated using the disk diffusion method.. Drug efficacy assessment was restricted only to patients with positive baseline culture results (n = 121). Of the isolated organisms, 96.9% were sensitive to netilmicin, whereas only 75.0% were sensitive to gentamicin (p = 0.00001). Netilmicin provided a broad-spectrum coverage comparable with that of ciprofloxacin, ofloxacin, and norfloxacin. Netilmicin also was more effective than gentamicin in eradicating infections (p = 0.001 at day 5 and p = 0.037 at day 10) and in ameliorating the CSS (p = 0.037 at day 3, p = 0.001 at both day 5 and day 10). Only minor adverse events occurred in patients treated with either netilmicin or gentamicin.. This study demonstrates that netilmicin is a safe and effective antibiotic that can be used as first-line therapy for the treatment of acute bacterial conjunctivitis.

Topics: Acute Disease; Administration, Topical; Anti-Bacterial Agents; Bacteria; Conjunctivitis, Bacterial; Cornea; Double-Blind Method; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Netilmicin; Prospective Studies; Safety

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Critical Care; Cross Infection; Drug Monitoring; Drug Therapy, Combination; Female; Gram-Positive Bacterial Infections; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Teicoplanin; Vancomycin

In a prospective, randomized trial, netilmicin given once daily (OD) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen (TD), both in combination with a broad spectrum beta-lactam, as initial empirical therapy for febrile neutropenic patients; the total daily dosage of netilmicin in each group was 6 mg/kg body weight. Twenty-nine of the 116 (25%) evaluable patients had microbiologically documented septicaemia, most of which were caused by Gram-positive bacteria, 41 (35%) had microbiologically documented infection without bacteraemia and 46 (40%) had possible infection. Highest peak serum concentrations of netilmicin in the OD group were significantly higher and trough serum concentrations significantly lower than in the TD group. A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome. The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy. Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment. The incidence of nephrotoxicity was low and did not differ significantly between groups. Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing, but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy.

Topics: Anemia, Aplastic; Anti-Bacterial Agents; beta-Lactams; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Neutropenia; Prospective Studies

Two randomized studies have been initiated to establish the role of teicoplanin as systemic therapy for infections in burns patients and as short-term prophylaxis for orthopaedic implant surgery. Opportunistic micro-organisms causing infections in burn patients are often acquired in hospital. These infections commonly involve Gram-positive organisms which may be resistant to several antibiotics. Teicoplanin, alone and in combination with additional antibacterial drugs, is effective in the treatment of Gram-positive infections of various types. In addition, teicoplanin has proved useful as prophylaxis against infection in orthopaedic surgery. Deep prosthetic infections are very difficult to cure without removing the infected device; the outcome can be devastating, such as total loss of joint function, amputation, and, occasionally, death. Preliminary results from the two studies are encouraging and show that teicoplanin has a role to play both in treatment of infection and as prophylaxis against hospital-acquired infection.

Topics: Adult; Burns; Cefazolin; Cross Infection; Drug Therapy, Combination; Female; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Joint Prosthesis; Male; Middle Aged; Netilmicin; Postoperative Complications; Teicoplanin; Thymus Extracts; Wound Infection

Topics: Azlocillin; Ciprofloxacin; Drug Therapy, Combination; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Netilmicin; Neutropenia; Prospective Studies

Aminoglycosides are recommended for the treatment of Enterococcus faecalis infections, especially in severe and bacteremic infection. However, the optimal aminoglycoside or the optimal dosage remains uncertain. This study aimed to compare the activity of four aminoglycosides against E. faecalis (gentamicin, netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical strain of E. faecalis was used to induce aortic endocarditis in the study rabbits. Each aminoglycoside was infused daily over 3 days with a computer-regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6 mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin. Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were compared over 1 or 3 days of treatment. The in vivo efficacy was assessed according to the bacterial count in vegetations, in comparison with a control group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed significant antibacterial efficacy after 3 days of treatment. After only 1 day of treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin showed the best efficacy, with the best results after 24 h of treatment for the highest dosage.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Bacterial Load; Disease Models, Animal; Drug Administration Schedule; Drug Evaluation, Preclinical; Endocarditis, Bacterial; Enterococcus faecalis; Female; Gentamicins; Gram-Positive Bacterial Infections; Netilmicin; Rabbits; Time Factors; Tobramycin

The clinical behavior and optimal treatment of relapsing and recurrent peritonitis episodes in patients undergoing long-term peritoneal dialysis are poorly understood.. Retrospective study over 14 years.. University dialysis unit; 157 relapsing episodes (same organism or culture-negative episode occurring within 4 weeks of completion of therapy for a prior episode), 125 recurrent episodes (different organism, occurs within 4 weeks of completion of therapy for a prior episode), and 764 control episodes (first peritonitis episode without relapse or recurrence).. Exit-site infection, empirical antibiotics.. Primary response (resolution of abdominal pain, clearing of dialysate, and peritoneal dialysis effluent neutrophil count < 100 cells/mL after 10 days of antibiotic therapy), complete cure (resolution by using antibiotics without relapse/recurrence), catheter removal (for any cause while on antibiotic therapy), and mortality.. Compared with the control group, more relapsing episodes were caused by Pseudomonas species (16.6% versus 9.4%) and were culture negative (29.9% versus 16.4%); recurrent infections commonly were caused by Enterococcus species (3.2% versus 1.2%) or other Gram-negative organisms (27.2% versus 11.1%) or had mixed bacterial growth (17.6% versus 12.7%). There were significant differences in primary response, complete cure, and mortality rates among groups (P < 0.001 for all comparisons). Compared with the control and relapsing groups, post hoc analysis showed that the recurrent group had a significantly lower primary response rate (86.4%, 88.5%, and 71.2%, respectively), lower complete cure rate (72.3%, 62.4%, and 42.4%, respectively), and higher mortality rate (7.7%, 7.0%, and 20.8%, respectively).. Retrospective analysis.. Relapsing and recurrent peritonitis episodes are caused by different spectra of bacteria and probably represent 2 distinct clinical entities. Recurrent peritonitis episodes had a worse prognosis than relapsing ones.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefazolin; Ceftazidime; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Logistic Models; Male; Middle Aged; Netilmicin; Peritoneal Dialysis; Peritonitis; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Vancomycin

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.

Topics: Aged; Anti-Bacterial Agents; Endocarditis, Bacterial; Equipment Contamination; Gentamicins; Gram-Positive Bacterial Infections; Hearing Loss, Sensorineural; Humans; Male; Netilmicin; Pacemaker, Artificial

Enterococci with gentamicin MICs of 256 to 1,024 micrograms/mL were evaluated for susceptibility to ampicillin plus gentamicin synergism. Sixteen of eighteen enterococcal isolates were not susceptible to synergistic killing by ampicillin plus gentamicin; 11 possessed aac(6')-aph(2"), and 4 possessed aph(2")-Ic. A gentamicin MIC of 512 or 1,024 micrograms/mL predicted lack of ampicillin/gentamicin synergism, but a gentamicin MIC of 256 micrograms/mL did not. For six enterococcal strains possessing the gentamicin-resistance gene aph(2")-Ic, ampicillin plus dibekacin, ampicillin plus netilmicin, and ampicillin plus amikacin produced synergistic killing in five, three, and two strains, respectively.

Topics: Amikacin; Ampicillin; Animals; Dibekacin; DNA Primers; DNA Probes; DNA Restriction Enzymes; Drug Resistance, Microbial; Drug Synergism; Electrophoresis, Agar Gel; Enterococcus faecium; Gentamicins; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Netilmicin; Penicillins; Polymerase Chain Reaction

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Computer Simulation; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Gentamicins; Gram-Positive Bacterial Infections; Half-Life; Humans; Netilmicin; Penicillins; Vancomycin