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PubMed1987

[Susceptibility of gram-negative bacilli to aminoglycosides].

In this study, the antibiotic sensitivity results of some gram-negative bacilli to aminoglycosides have been presented. 704 E. coli, 152 Klebsiella, 158 Proteus, 155 Pseudomonas strains were examined. These bacilli were isolated from the clinical samples at the bacteriology lab.in Ibni Sina Hospital, between January 1986-January 1987. The percents of E. coli strains susceptible to gentamicin, tobramycin, netilmicin and amikacin were 74%, 84%, 90%, 85% respectively. The sensitivity pattern of Proteus strains to the same antibiotic at the same order was 45%, 57%, 68, 84%. On the other hand 52%, 61%, 87%, 92% of Klebsiella strains and 32%, 53%, 86%, 81% of Pseudomonas strains have been found to be susceptible to gentamicin, tobramycin, netilmicin and amikacin respectively. According to these results, the resistance of gram-negative bacilli to aminoglycosides (including amikacin) is relatively high in our hospital, but amikacin or netilmicin should be preferred to others in which cases aminoglycoside therapy is considered.

Aminoglycosides↗

PubMed1985

In vitro antibacterial activity of imipenem against Pseudomonas and Staphylococcus species. Comparison with thirteen other antimicrobial agents.

The in vitro antimicrobial activity of imipenem against recent clinical isolates of Pseudomonas spp. (94 strains) and penicillin-resistant Staphylococcus spp. (50 Staph. aureus and 50 coagulase-negative Staphylococcus) was assessed using the Mueller-Hinton agar dilution method. Results were compared with those simultaneously obtained for amikacin, netilmicin, tobramycin, norfloxacin, piperacillin, ceftazidime, ceftriaxone and azthreonam against Pseudomonas spp., and for rifampicin, clindamycin, netilmicin and cefoxitin, besides penicillin and methacillin, against Staphylococcus spp. About 50 and 90% of 84 Pseudomonas aeruginosa isolates were inhibited by concentrations of imipenem equal to or less than 2 and 8 mg/l respectively. The in vitro activity of imipenem was comparable to that of ceftazidime and norfloxacin, but superior to that of the aminoglycosides and all the other antibiotics tested, in terms of potency by weight. Among other Pseudomonas spp. only P. malthophilia (2 strains) proved resistant to imipenem. Rifampicin was the most active antibiotic by weight against Staph. aureus but imipenem was more active than clindamycin and, especially, netilmicin and cefoxitin. Imipenem was highly active also against coagulase-negative staphylococci, with some differences related to the high incidence of methicillin-resistant strains. MICs of imipenem in Mueller-Hinton broth correlated with those obtained in agar, unlike the aminoglycosides. There were no significant inoculum effects on MICs of imipenem and MBCs were within one twofold dilution of MICs in over 75% of assays.

Aminoglycosides↗

PubMed1977

Antimicrobial susceptibility of gentamicin-resistant Pseudomonas aeruginosa.

The susceptibility of 41 strains of gentamicin-resistant Pseudomonas aeruginosa to tobramycin, sisomicin, netilmicin, amikacin, and carbenicillin was determined. Amikacin and carbenicillin exhibited the greatest activity against these strains and especially against those with a high level of resistance to gentamicin. Netilmicin exhibited little activity, whereas tobramycin and sisomicin were active against approximately two-thirds of the strains. Cross-resistance to tobramycin, sisomicin, and netilmicin was frequent.

Amikacin↗

PubMed1995

The most frequently occurring aminoglycoside resistance mechanisms--combined results of surveys in eight regions of the world. The Aminoglycoside Resistance Study Groups.

Aminoglycoside-resistant isolates from different patients were collected in 149 hospitals in eight regions of the world. Aminoglycoside resistance mechanisms were determined in 11,079 of these isolates by the correlation of resistance phenotypes to 12 aminoglycosides and DNA hybridisation with up to 19 resistance genes. A very large diversity of different resistance mechanisms was found. For example, in Escherichia-Morganella-Proteus-Salmonella-Shigella, at total of 53 different mechanisms was found among the 2080 isolates studied. Therefore, the most common resistance mechanisms in the seven different pathogen groups were summarised. The seven pathogen groups were chosen so that each one had a unique mixture of resistance mechanisms. Among Enterobacteriaceae, the Citrobacter-Enterobacter-Klebsiella, Providencia and Serratia groups had a particularly high incidence of combinations of resistance mechanisms especially when compared with data from eight early surveys. These mechanisms often tended to be combinations of previously common gentamicin-modifying enzymes with AAC(6')-I, an enzyme which can acetylate tobramycin, netilmicin and amikacin but which does not usually cause resistance to isepamicin. Resistance rates among the four Enterobacteriaceae groups reflected the incidence of these combinations; that is, amikacin resistance was 43.1%, 21.7%, 4.2% and 37.6% while that to isepamicin was 9.9%, 9.7% 2.7% and 7.6%, respectively. A very large diversity of mechanisms was found in Pseudomonas. However, three mechanism - permeability, ACC(6')-II and ANT(2")-I - were very common, both alone as single mechanisms and in combination with each other or other mechanisms. Because of the high incidence of permeability resistance in Pseudomonas, resistance to all aminoglycosides was quite high and the difference between amikacin (41.7%) and isepamicin (36.8%) was smaller. The greatest diversity of resistance mechanisms (67 in 1189 isolates) was found in Acinetobacter. The most common mechanisms - APH(3')-VI and AAC(3)-? - were generally very rare in other genera but found frequently in Acinetobacter in combinations with a wide variety of other mechanisms. The most frequent resistance mechanisms in Acinetobacter varied by geographic region much more than did mechanisms in other genera. The resistance rates to all of the clinically useful aminoglycosides were generally higher in Acinetobacter than in any other pathogen group. In contrast to the other pathogen groups, only seven resistance mechanisms were found in the 898 resistant Staphylococcus. These were composed of the three known single mechanisms and four combinations of these three mechanisms. Because the principal resistance mechanism, (APH(2") + ACC(6'), confers high-level resistance to gentamicin and tobramycin and a lower level of resistance to amikacin, isepamicin and netilmicin, the observed resistance rate to netilmicin (15.0%) was the lowest for any of the aminoglycosides.

Acetyltransferases↗

PubMed2003

A new micellar electrokinetic capillary chromatography method for separation of the components of the aminoglycoside antibiotics.

Aminoglycoside antibiotics are always a mixture of structurally related amino sugars, which do not have a chromophore or fluorophore. The aim of the study was to find one method for evaluation of the components and impurities of the antibiotics. Derivatization with o-phthaldialdehyde and thioglycolic acid is found to be appropriate for all antibiotics. The components of gentamicin (GM), sisomicin, netilmicin, kanamycin, amikacin, and tobramycin were tried to separate by means of micellar electrokinetic chromatography. The background electrolyte was composed of sodium tetraborate (100 mM, pH 10.0), sodium deoxycholate (20 mM), and beta-cyclodextrin (15 mM). This method is valid for evaluation of GM, kanamycin, and tobramycin. It has to be improved for amikacin and netilmicin. In addition, 46 bulk samples of GM of different manufacturer or pharmaceutical companies were investigated. Many samples were found to contain many minor products and different amounts. Beside different patterns of the main compounds GM C1, GM C1a, GM C2a, and GM C2, many lots were found consisting of a substantial number of minor products. The appearance of a high number of minor products is always associated with the existence of sisomicin, which is not found in "pure" samples. However, almost all samples met the requirements of the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP).

Amikacin↗

PubMed1986

Antibiotic stability in an implantable pump.

We measured the stability of vancomycin, amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam in an implantable drug pump. Two pumps were filled with the antibiotic being tested and were incubated at 37 degrees for 3 weeks. Samples were taken daily. At 3 weeks the pumps were disassembled and examined microscopically for signs of deterioration. If the pumps were intact, bioassays were used to quantitate the biologic activity of each daily antibiotic sample. Vancomycin degraded the pump. Amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam had no effect on the pump and maintained their biologic activity over the 3-week period.

Amikacin↗

PubMed1990

Shifts in auditory brainstem response latencies following plasma-level-controlled aminoglycoside therapy.

The ototoxic effect of plasma-level-controlled netilmicin and tobramycin was monitored in 20 intensive care patients, using auditory brainstem responses (ABRs). ABRs were recorded at the onset and after 6 days of treatment. Significant shifts in the ABR wave V latency were observed independent of the type of medication received or whether the patients were intubated or not. Shifts were also observed in wave I latencies. These latter changes were only significant for the complete population, probably because this potential is more difficult to elicit and measure than is wave V. The I-V interlatency time was greater for netilmicin than for tobramycin. These results indicate that the cumulative effects of aminoglycoside ototoxicity may be different for the central and peripheral nervous systems, and therefore ABR measurements may be the most accurate way of controlling ototoxicity in intensive care patients.

Adult↗

PubMed1988

Three-year survey of amikacin use and aminoglycoside resistance in a general hospital in Belgium.

The aim of the study was to evaluate the effect of intensive use of amikacin on the resistance levels to amikacin, gentamicin, tobramycin, netilmicin and dibekacin. The base-line resistance in the preamikacin phase (three months of amikacin use less than 1%; 676 isolates) was 1.0% for amikacin, 11.4% for gentamicin, 8.0% tobramycin, 6.2% for netilmicin and 8.3% for dibekacin. During the amikacin phase (36 months of average amikacin use of 89%; 6048 isolates) there was no significant change in aminoglycoside resistance except for dibekacin (from 8.3% to 10.9%, 0.05 greater than p greater than 0.02). Isolated amikacin resistance was not observed.

Amikacin↗

PubMedDate not supplied

Cost-effectiveness of ceftazidime or imipenem/cilastatin versus ceftriaxone + aminoglycoside in the treatment of febrile episodes in neutropenic cancer patients in Germany.

A three-pronged cost-effectiveness analysis of the treatment of febrile episodes in neutropenic cancer patients was conducted. It included a review of 37 randomized, controlled studies in the MEDLINE and EMBASE databases (1980-1996). Clinical outcomes as well as costs of treatment with imipenem/cilastatin, ceftazidime and ceftriaxone + aminoglycoside were compared. Primary therapy and modification, respectively, were successful in 62 and 27% of patients treated with imipenem/cilastatin, in 56 and 31% with ceftazidime and in 41 and 13% with ceftriaxone + aminoglycoside. From the perspective of a 1,800-bed teaching hospital, the average overall cost per successfully treated patient was DM 7,475 with imipenem/cilastatin, DM 7,810 with ceftazidime and DM 8,963 with ceftriaxone + netilmicin (DM 1 = USD 0.56; 7/97). The costs for the German national economy were imipenem/cilastatin DM 23,828, ceftazidime DM 24,985 and ceftriaxone + netilmicin DM 29,838.

Ceftazidime↗

PubMed1985

Comparative toxicity of intravitreal aminoglycoside antibiotics.

We compared the toxicity of the aminoglycoside antibiotics (tobramycin, amikacin, netilmicin, and kanamycin) by ophthalmoscopy, light and electron microscopy, and electro-retinography after intravitreal injection in rabbits in doses ranging from 100 to 3,000 micrograms. The earliest manifestations of toxicity were confined to the outer retina with each drug, with lamellar lysosomal inclusions in the retinal pigment epithelium as the earliest finding. However, the aminoglycosides displayed marked differences in the threshold dose required to produce toxic reactions, permitting the following ordering of toxicity: (most toxic) gentamicin greater than netilmicin = tobramycin greater than amikacin = kanamycin (least toxic).

Amikacin↗

PubMed1987

The effects of in vivo antibiotics on neutrophil (PMN) activity in rabbits with peritonitis.

Antibiotics play an important role in helping the host fight infection; however, the direct cellular effect of antibiotics on polymorphonuclear cells remains undefined. Adherence, chemotaxis, phagocytosis, and superoxide anion production are important steps in the cascade of events initiated by the polymorphonucleocyte in bacterial killing. Previous studies have shown inhibition as well as stimulation of neutrophil antibacterial therapy by antibiotics. Peritoneal and blood polymorphonuclear neutrophils (PMN) respond differently to peritonitis and to external agents. The purpose of this study was to investigate the effects of in vivo clindamycin and netilmicin on infected rabbit peritoneal and blood polymorphonuclear adhesiveness, phagocytosis, chemotaxis, and superoxide anion production. Peritoneal and blood PMNs were obtained from rabbits which had undergone appendiceal devascularization 18 hr earlier: antibiotics were administered intramuscularly 1 hr prior to appendectomy and every 8 hr postoperatively for 5 days; these PMNs were compared to infected rabbits which did not receive antibiotics. Clindamycin and netilmicin in vivo cause significant inhibition of phagocytosis, peritoneal adhesiveness, and, when used in combination, blood adhesiveness and peritoneal superoxide anion production. No effects were seen on chemotaxis. Based on this data we conclude that antibiotics, while vitally important in fighting infections, may in and of themselves be agents of immunosuppression at the cellular level.

Animals↗

PubMed1986

In vitro interactions between teicoplanin and other antibiotics against enterococci and staphylococci.

In this study we have evaluated the in vitro activity of teicoplanin, a potent anti-staphylococcal and anti-enterococcal agent, in combination with rifampicin, netilmicin, amikacin, fosfomycin and imipenem. Drug interactions were assessed using a microtitre checkerboard dilution method and a time-kill test. With rifampicin, indifference or an additive effect was the prevalent outcome with both methods. With netilmicin and amikacin synergism was seen against half of the enterococcal strains, whereas indifference was more common with staphylococcal isolates. Synergism predominated when teicoplanin was combined with fosfomycin and imipenem. Under no circumstances and with no combination of drugs were we able to detect antagonistic effects.

Amikacin↗

PubMed1991

Synergistic antibacterial interaction of cefotaxime and desacetylcefotaxime.

Cefotaxime (CTX) is metabolized in desacetylcefotaxime (dCTX), a less potent compound which shows, however, a higher stability against selected beta-lactamases produced by Gram-negative organisms. The aim of this study was to verify if the antimicrobial activity of CTX against 260 clinical aerobic and anaerobic pathogens isolated in our institution was enhanced by its metabolic derivative dCTX. The combination of CTX and dCTX, assessed by checkerboard titration, was completely or partially synergistic towards 61% of the 220 aerobic organisms tested and against 68% of the 40 Bacteroides strains analyzed. In addition we have investigated, by the time-kill method, the in-vitro interactions against 50 aerobic strains of CTX and dCTX alone and in combination with netilmicin, a drug often employed in severe infections in combination with beta-lactam agents in order to provide effective killing of resistant nosocomial pathogens. Time-kill studies indicated that 36% of the aerobic nosocomial strains were synergistically inhibited by the combination of CTX/dCTX with netilmicin. These results indicate that dCTX makes an important contribution to the clinical efficacy of CTX.

Bacteria↗

PubMed1992

In vitro interactions of aminoglycosides with imipenem or ciprofloxacin against aminoglycoside resistant Acinetobacter baumannii.

The in vitro interactions between gentamicin, tobramycin, netilmicin and amikacin with imipenem and ciprofloxacin were evaluated by the killing curve technique against 20 clinical isolates of Acinetobacter baumannii highly resistant to aminoglycosides which were susceptible or moderately susceptible to imipenem and resistant or moderately susceptible to ciprofloxacin. Imipenem enhanced killing by gentamicin, tobramycin, netilmicin and amikacin in tests with 9, 12, 10 and 15 strains (45-75%) while ciprofloxacin with 3, 7, 5 and 6 strains (15-35%) respectively. Interaction results were influenced by the height of aminoglycoside minimum bactericidal concentrations (MBCs) but were independent of imipenem or ciprofloxacin MBCs and the presence of aminoglycoside modifying enzymes. It is concluded that enhanced killing after aminoglycoside interaction with imipenem or ciprofloxacin versus A. baumannii cannot be predicted but it should be carefully tested in vitro. The in vivo significance of the reported findings mandates clinical studies in humans.

Acinetobacter↗

PubMed2005

Cortical allograft as a vehicle for antibiotic delivery.

BACKGROUND: Infection can be a devastating complication after implantation of a cortical bone allograft. The allograft could act as a vehicle for local antibiotic prophylaxis. MATERIAL AND METHODS: We studied the release of antibiotics in vitro from cortical bone allografts impregnated with antibiotics for different periods of time. We also studied whether cortical allografts impregnated with antibiotics could eradicate Staphylococcus aureus from an experimentally infected graft in vivo. In the in vitro study, pieces of cortical bone were impregnated with netilmicin, vancomycin, ciprofloxacin and rifampicin for 1 h, 10 h and 100 h. The antibiotics were eluted into phosphate-buffered saline (PBS) for 7 days, with daily transfer of the bone into fresh PBS. In the in vivo study, cortical allografts impregnated with antibiotics were placed in rats intramuscularly. 10 microL of an S. aureus suspension (0.6 x 10(5) CFU) was placed in the intramedullary cavity. After 15 days, the allografts were removed and examined for bacterial growth. RESULTS: The amount of antibiotics released in vitro was influenced by the time used for antibiotic impregnation of the bone. Allografts impregnated with netilmicin, vancomycin and rifampicin effectively eradicated perioperative contamination with S. aureus in vivo. INTERPRETATION: This study shows that a cortical bone allograft would be an effective vehicle for local antibiotic delivery.

Animals↗

PubMed1984

The key role of aminoglycosides in antibacterial therapy and prophylaxis.

The discovery that aminosugars found in nature kill common bacteria initiated use of a new class of antibiotics that have played a key role in the management of several major medical problems over the past 40 years. The rapid bactericidal effect of the aminoglycosides on aerobic Gram-negative bacilli has expanded their use to approximately 6% of all our general hospital patients. These agents have many desirable properties, but also have the potential for producing ototoxicity and nephrotoxicity that imposes pharmacological limitations on their optimum use. The experience of earlier investigations demonstrated the need for quantitative measurements and individual patient dosing which has reduced the risk of toxicity many fold. Using sensitive measurements, toxic manifestations can be classified as detectable by laboratory means only, some that have clinical expression and rarely a lasting handicap. Semisynthetic modification of kanamycin (amikacin) and sissomicin (netilmicin) protects these compounds against inactivation by most bacterial enzymes and preserves their effectiveness. Netilmicin seems to have less potential for causing toxicity, especially ototoxicity that is irreversible, and offers the possibility of further gains through pharmacological flexibility without crippling toxicity.

Aminoglycosides↗

PubMed1984

Recent otological evaluation of aminoglycoside antibiotics.

A survey is made of comparative studies of ototoxicity of different aminoglycoside antibiotics. Animal studies show clearly lower netilmicin ototoxicity compared with that of other aminoglycoside antibiotics. Clinical controlled comparative trials are few. Most studies have few patients in each group. The significance of auditory threshold shifts in single frequencies as criteria of ototoxicity is uncertain. An analysis of clinical and animal studies together indicates, however, that netilmicin has a higher ratio of efficacy to ototoxicity than other aminoglycoside antibiotics.

Aminoglycosides↗

PubMed1990

Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity?

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.

Audiometry↗