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PubMed1984

The clinical versatility of aminoglycosides.

The value of netilmicin, like that of other antibiotics, is influenced by its antimicrobial specificity, dosage and ease of administration, activity in pus and the underlying condition of the host. Different classes of antibiotics and different members among a group of antibiotics have relative strengths and weaknesses among these clinical factors that affect the results of antibacterial therapy and must be determined by careful clinical investigation.

Aminoglycosides↗
PubMed1984

Inhibition of mammalian microsomal protein synthesis by aminoglycoside antibiotics.

The aminoglycoside antibiotics gentamicin, kanamycin and netilmicin produce a dose-dependent inhibition of amino acid incorporation in microsomes isolated from human liver and rat brain, kidney and liver. Inhibitory effects on microsomal protein synthesis occur at concentrations that have been shown to accumulate in rodent and human renal cortex and perilymph following therapeutic administration. Inhibition of translation in those tissues which specifically accumulate aminoglycoside antibiotics may, in part, explain toxicities observed following exposure to aminoglycosides.

Aminoglycosides↗
PubMed1986

Antibiotic prophylaxis in vascular reconstructive surgery: a double-blind placebo-controlled study.

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

Adolescent↗
PubMed1986

Selective growth of resistant variants during incubation of Enterobacteriaceae with four aminoglycosides.

The selective growth of resistant variants, present at low frequencies, varied with different strains of Enterobacteriaceae and different aminoglycosides. This phenomenon was more pronounced during incubation with amikacin than with gentamicin, netilmicin and tobramycin. Selective growth of the resistant variants resulted in an inoculum effect and an increase in MIC with longer incubation. In-vitro evaluation of this phenomenon may be justified when choosing an aminoglycoside for therapy.

Adenosine Triphosphate↗
PubMed1986

Intravenous ciprofloxacin in the treatment of infection in immunocompromised patients.

We initially used ciprofloxacin to treat immunocompromised patients whose fever had failed to respond or had recurred in spite of multiple broad-spectrum antibiotics. Results in this group encouraged us to proceed with a randomized trial of ciprofloxacin plus benzylpenicillin versus our standard empirical regimen of netilmicin and piperacillin for the treatment of fever in immunocompromised patients. Although the numbers of patients in this study are at present too small for comparison to be made, the favourable results seen in the refractory treatment group appear to be borne out so far in those receiving ciprofloxacin as first-line therapy.

Adolescent↗
PubMed1988

A mouse model for simultaneous pharmacokinetic and efficacy studies of antibiotics at sites of infection.

Tissue penetration may be an important pharmacokinetic determinant to achieve the chemotherapeutic efficacy of antimicrobial agents. We describe a mouse model for the simultaneous study of antibiotic kinetics and efficacy at the site of infection. With the doses tested there was no difference in drug penetration into healthy tissue and tissue at the site of acute bacterial infection. Ampicillin and netilmicin levels over the minimal inhibitory concentration (MIC) were needed to produce significant bacterial killing. During the 6 h observation period susceptible Gram-positive bacteria were eradicated whereas Gram-negative bacteria were reduced in number but not eradicated, even though the antibiotic concentrations exceeded minimal bactericidal concentration (MBC) three times.

Ampicillin↗
PubMed1988

Cloning and characterization of an AAC(6') gene from Serratia marcescens.

A gene encoding AAC(6') mediated resistance to netilmicin and amikacin was cloned from the chromosome of a nosocomial strain of Serratia marcescens into the BamHI site of pACYC184. The resistance determinant was localized to a sequence of approximately 1 kb. A 490 base pair BamHI-PvuII restriction fragment from the cloned DNA was used as a probe in Southern hybridization studies. Homology with a 920 base pair fragment of PvuII digested S. marcescens DNA from AAC(6')-producing strains was observed. No homology was detected with aminoglycoside sensitive S. marcescens or Escherichia coli.

Acetyltransferases↗
PubMed1989

In-vitro activity of the new penems FCE 22101 and FCE 24362 alone or in combination with aminoglycosides against streptococci isolated from patients with endocarditis.

Seven strains of viridans streptococci isolated from patients with endocarditis were inhibited in vitro by 0.06-2 mg/l and 0.016-0.5 mg/l of the penems FCE 22101 and FCE 24362 respectively. The MBCs were the same or two-fold higher than the respective MIC with three exceptions. One strain of Streptococcus faecalis was only inhibited (8 mg/ml respectively 0.5 mg/l; MBC greater than 32 mg/l) and one strain of Str. faecium was resistant (MIC greater than or equal to 16 mg/l). When combined with gentamicin or netilmicin a bactericidal and synergistic killing was observed within 1-8 h in all strains except Str. faecium. Synergy could also be confirmed in all cases by following bacterial growth kinetics after elimination of antibiotics, by calculating the difference between the times required for bacteria exposed to antibiotic and unexposed bacteria to increase in numbers (PAE).

Anti-Bacterial Agents↗
PubMed1989

Antibiotic exposure delays intestinal colonization by Clostridium difficile in the newborn.

Two antibiotic regimens commonly used in neonatal intensive care were compared for the rate at which Clostridium difficile appeared in the faeces. Over a nine month period neonates with suspected sepsis admitted to a Special Care Baby Unit (SCBU) were randomly allocated to receive either cefotaxime or penicillin and netilmicin. A contemporaneous group also admitted to SCBU but without sepsis served as non-treated controls. Four hundred and sixteen stool specimens from 158 neonates without diarrhoea were analysed every five to seven days until discharge. The results showed that these antibiotics did not encourage gut colonization by C. difficile, that they might even be protective in this respect and that monotherapy with cefotaxime was no more likely to generate C. difficile overgrowth than the penicillin-aminoglycoside regimen.

Anti-Bacterial Agents↗
PubMed1996

pH modulation of aminoglycoside resistance in Staphylococcus epidermidis harbouring 6'-N-aminoglycoside acetyltransferase.

The kinetic constants of the aminoglycoside-modifying enzyme 6'-N-aminoglycoside acetyltransferase (AAC(6')IV) from the clinical strain Staphylococcus epidermidis RYC 13036 differed depending on whether tobramycin and amikacin (glycosamine group) or gentamicin and netilmicin (garosamine group) were used as substrates. Acetylation of the glucosamine antibiotics was highly susceptible to substrate inhibition which increased with pH whereas the garosamine group compounds showed limited substrate inhibition over a wide pH range. These differences in activity correlated with MIC values of S. epidermidis RYC 13036 for different aminoglycosides. Aminosugars moiety and pH markedly influenced the AAC(6')IV-aminoglycoside interactions.

Acetyltransferases↗
PubMed2005

Molecular and phenotypic features for identification of the opportunistic pathogens Ochrobactrum spp.

Among the six species characterized within the genus Ochrobactrum, Ochrobactrum anthropi and Ochrobactrum intermedium are currently reported as opportunistic pathogens in humans. Since the species identification is mainly based on 16S rDNA analysis, the aim of this study was to search for other characteristics useful for Ochrobactrum species discrimination. Ribotyping, morphological and biochemical analyses, and antimicrobial susceptibility testing were performed for a panel of 35 clinical isolates, first identified to the species level using 16S rDNA sequencing. Type and reference strains of five Ochrobactrum species were comparatively analysed. Commercial identification systems such as API 20NE and VITEK 2 were tested for their ability to identify Ochrobactrum anthropi and to detect other members of the genus Ochrobactrum. An improved protocol for the identification of Ochrobactrum spp. by routine medical microbiology practices is proposed: isolation of a non-fastidious non-fermenting oxidase-positive Gram-negative rod resistant to all beta-lactams except imipenem indicates the genus Ochrobactrum, and the API 20NE system confirms the genus identification for most strains, whereas the VITEK 2 system using ID-GNB cards was less powerful. Urease activity, the mucoidy of the colonies, growth at 45 degrees C on tryptic soy agar, and susceptibility to colistin, tobramycin and netilmicin should be considered as differential characteristics for identification of O. anthropi and O. intermedium to the species level. However, definitive identification depends on genotyping methods.

Anti-Bacterial Agents↗
PubMed1986

Reliability of a disk diffusion method using semiconfluent growth in the determination of aminoglycoside resistance.

Susceptibility of 553 blood culture isolates to gentamicin, tobramycin, amikacin, and netilmicin was determined by a routine disk diffusion method with semiconfluent growth (AB Biodisk, Solna, Sweden) and a microtiter-method (Sensititre). The disk diffusion test gave false sensitive results in 9.4-71% of the 9-39 aminoglycoside resistant strains studied. False resistant results occurred in 1.0-7.6% of measurements among the over 500 aminoglycoside sensitive strains. Because of the frequent error rate, the disk method with semiconfluent growth should be replaced with other methods in the determination of aminoglycoside resistance in bacteriological laboratories.

Amikacin↗
PubMed1986

Antibiotic susceptibility of Haemophilus influenzae isolated from cerebrospinal fluid and blood.

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

Anti-Bacterial Agents↗
PubMed1991

Mechanisms of lipofuscinogenesis: effect of the inhibition of lysosomal proteinases and lipases under varying concentrations of ambient oxygen in cultured rat neonatal myocardial cells.

The objective of this study was to analyse the relative roles of oxidative stress and lysosomal lytic enzymes in lipofuscin formation in cultured neonatal rat cardiac myocytes. Myocytes were exposed to E-64 (an inhibitor of lysosomal cathepsins L. D and H), netilmicin (an inhibitor of lysosomal phospholipases A1 and C) and leupeptin (an inhibitor of cytosolic and lysosomal thiolproteinases) under varied conditions of oxidative stress (20% and 40% ambient oxygen) for up 14 days. Lipofuscin was quantified by microspectrofluorometry. The amount of lipofuscin accumulation was enhanced by the lytic enzyme inhibitors as well as by the increase in the ambient oxygen concentration. However, the effects of enzyme inhibitors was less obvious under 40% ambient oxygen than under 20% oxygen. Data are interpreted as suggesting that, under high levels of oxidative stress, intralysosomal peroxidative changes related to lipofuscin formation occur so rapidly that lytic activity assumes a minor role in lipofuscinogenesis whereas, under low oxidative stress, inhibition of lytic activity makes a greater contribution to lipofuscinogenesis by allowing a longer period of time for peroxidative changes. The results further substantiate the hypotheses that (a) lipofuscinogenesis is strongly related to oxidative stress, and (b) lipofuscin forms intralysosomally as a result of processes involving incomplete degradation of heterophagocytosed and or autophagocytosed material.

Animals↗
PubMed2005

Pyometra in a bitch following unusual sterilisation.

A female, stray crossbreed dog, approximately four years old, was presented for routine spaying during a charity neutering programme in Romania. On clinical examination the bitch was lethargic and pyrexic (40.6 degrees C), but no other signs of illness were detected. Laparotomy revealed an enlarged uterus, severed at the cervix, with no communication to the vagina. Abdominal inspection showed an apparently normal, ligated vaginal stump. An ovariohysterectomy was performed and the dog was treated with a seven-day course of netilmicine. It subsequently made a full recovery.

Animals↗
PubMed1978

Aminoglycoside antibiotics moderately impair granulocyte function.

By in vitro methods, five aminoglycoside antibiotics (amikacin, kanamycin, gentamicin, tobramycin, and netilmicin) were shown to produce modest changes in granulocyte adherence (increase) and migration (decrease) and no change in phagocytosis or nitroblue tetrazolium reduction.

Amikacin↗
PubMed1985

Effects of aminoglycoside antibiotics on polymorphonuclear leukocyte function in vivo.

In vitro incubation of aminoglycoside antibiotics with human polymorphonuclear leukocytes (PMNs) has been shown to induce abnormalities in cell function. This study was designed to determine whether there are similar abnormalities in leukocyte function after exposure to the action of these agents in vivo. Four aminoglycosides (gentamicin, tobramycin, netilmicin, and amikacin) were tested. In vitro incubation did not induce a chemotactic defect when measured by an under-agarose method. However, inhibition of candidacidal activity was reproducible after in vitro incubation of all aminoglycosides tested. Nevertheless, when the aminoglycosides were administered intravenously to normal volunteers, PMN function, including adherence to nylon wool columns, chemotaxis, phagocytosis, and killing of Candida albicans, was unimpaired at 1, 3, and 24 h postinfusion. Therefore, we conclude that aminoglycoside antibiotic administration does not induce PMN dysfunction in vivo.

Adult↗
PubMed1986

Effect of NaCl supplementation of Mueller-Hinton broth on susceptibility of staphylococci to aminoglycosides.

The addition of NaCl to cation-supplemented Mueller-Hinton broth increased the MICs of gentamicin, amikacin, and netilmicin for coagulase-positive and -negative staphylococci in a concentration-dependent manner. At 2% NaCl, geometric mean MICs were elevated 14.1- to 25.6-fold. Mueller-Hinton broth containing added NaCl should not be used for testing the susceptibility of staphylococci to aminoglycosides.

Amikacin↗