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PubMed1978

1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides.

1-N HAPA gentamicin B is a new aminoglycoside active against most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Among 504 clinical isolates at a concentration of 12.5 microgram/ml all Staph. aureus, Escherichia coli, Klebsiella, Enterobacter, Proteus rettgeri, Providencia and 78% of Pseudomonas, 86% of Proteus morganii were inhibited. Like other aminoglycosides, the activity was greatest at an alkaline ph and reduced by high cations concentrations. 1-N HAPA gentamicin B was equal in activity to amikacin against both gentamicin-sensitive and resistant isolates. It inhibited bacteria containing many of the aminoglycoside inactivating enzymes. When combined with carbenicillin it inhibited in a synergistic manner many Gram-negative bacteria, particularly Pseudomonas and Serratia.

Aminoglycosides↗
PubMed1978

The syntheses and biological properties of 1-N-(S-4-amino-2-hydroxybutyryl)-gentamicin B and 1-N-(S-3-amino-2-hydroxypropionyl)-gentamicin B.

The syntheses of 1-N-(S-4-amino-2-hydroxybutyryl)-gentamicin B and 1-N-(S-3-amino-2-hydroxypropionyl)-gentamicin B, designated sch 20287 and Sch 21420, respectively, by procedures similar to those developed by KAWAGUCHI and co-workers for the transformation of kanamycin A to amikacin are described. The in vitro microbiological properties of Sch 20287 and Sch 21420 are compared with amikacin, gentamicin and tobramycin.

Bacteria↗
PubMed1992

[Immunochemical determination of gentamicin in serum. II. Preparation of polyclonal gentamicin antibodies].

The author describes the preparation of polyclonal rabbit antibodies against gentamicin. As immunogens gentamicin conjugates with bovine serum albumin were used, or else with thyroglobulin and haemocyanin. The immunization pattern involved combined administration of immunogens by the intravenous route, or by the intramuscular or intradermal route, using liposomes and complete Freund adjuvant. The highest antibody titres against gentamicin found by the ELISA method were obtained when procedures were used where the carrier was serum albumin and thyroglobulin and as adjuvant complete Freund adjuvant was used.

Animals↗
PubMed1989

[Studies of the effect of gentamicin on the kidneys of healthy young rats. II. Studies of renal parenchyma of experimental animals in the light and electron microscopy after gentamicin load].

Gentamicin was given to rats in the doses and intervals equivalent to those used in patients. This resulted in the morphologic changes in the animal kidneys. The severity of them was directly related to the dose of antibiotic. The morphologic changes--vacuolar degeneration in the epithelial cells of the proximal tubule, the inflammatory infiltrates in the interstitial tissue and the increased number of lysosomes with myelinic structures as well as mitochondrial oedema, the increased number of peroxysomes in the epithelial cells of the proximal tubules indicate the toxic influence of gentamicin on the proximal tubule. The disappearance of the morphologic and functional changes after the withdrawal of gentamicin indicates reversibility of them.

Age Factors↗
PubMed1989

A study of synergism between cloxacillin and gentamicin on resistant staphylococci (penicillinase producing and gentamicin resistant).

Twelve strains of Staphylococcus aureus were studied. All the strains were tested for penicillinase production by the iodometric and starch-paper methods. Ten out of 12 strains produced penicillinase. A strain which was gentamicin resistant and penicillinase producer was tested for synergism using the killing growth method. Synergism was observed between cloxacillin and gentamicin. These two antibiotics can now be used to treat infection by Staphylococcus aureus especially those that produce penicillinase and gentamicin resistant.

Cloxacillin↗
PubMed1977

Gentamicin assay by enzymatic adenylylation and the application of a double osmotic shock procedure to prepare gentamicin adenine mono-nucleotide transferase.

The release of gentamicin adenine mono-nucleotide transferase (GAdT) during single cold osmotic shock treatment of E. coli K12 W677/HJR66 is not always maximal. The yield of GAdT could not be improved by using E. coli harvested at different stages of growth, by prolonging the exposure to the different steps of the shock procedure, by changing the sucrose concentration, or the magnesium chloride volume. The quantity of GAdT in osmotic extracts could be increased when a double shock procedure was performed. Using an aliquot (30 microliter) of the extract, an accurate and quick assay for gentamicin, sisomicin and tobramycin in microvolumes of serum (30 microliter) can be accomplished. To avoid high background activity in the assay, the extracts should be prepared from E. coli grown in gentamicin-free medium.

Adenosine Triphosphate↗
PubMed2004

The in vitro elution of gentamicin sulfate from a commercially available gentamicin-loaded acrylic bone cement, VersaBond AB.

The present study was designed to yield results that would be used to contribute to the ongoing debate about the mechanism of the in vitro elution of an antibiotic from an antibiotic-loaded acrylic bone cement. To this end, the elution rates (R) of gentamicin sulfate (expressed as a weight percentage of the initial mass of the antibiotic in the specimen, normalized with respect to the duration of the test) from statically loaded (STATIC) and dynamically loaded (+/-10 MPa; 2 Hz; until fracture; DYNAMIC) specimens fabricated from a commercially available acrylic bone cement (VersaBond AB), in phosphate-buffered saline solution at 37 degrees C, were obtained with the use of a spectrophotometric method. There was evidence of microcracking in the fracture surfaces of DYNAMIC specimens, but no such evidence in the case of STATIC specimens. The surface area of the DYNAMIC specimens, during the tensile phase of the cyclical loading, was estimated to be about 3% larger than for the STATIC specimens (1742 mm(2) versus 1696 mm(2)). The bulk porosities P of the specimens in both sets were also determined and found to not be statistically different, with P for the STATIC and DYNAMIC specimens being 8.55 +/- 0.10 and 8.88 +/- 0.18%, respectively. At the end of the test period, R was found to be 0.36 +/- 0.20 and 1.28 +/- 0.14 wt %/day for the STATIC and DYNAMIC specimens, respectively. It is suggested that the present results provide support for the postulate that the elution mechanism of gentamicin in this cement is a surface phenomenon.

Bone Cements↗
PubMed1985

A comparison of pneumonia caused by gentamicin, methicillin-resistant and gentamicin, methicillin-sensitive Staphylococcus aureus: epidemiologic and clinical studies.

We investigated an outbreak of nosocomial pneumonia due to gentamicin, methicillin-resistant Staphylococcus aureus (GMRSA). We compared the predisposing factors for pneumonia due to GMRSA to those for pneumonia due to gentamicin, methicillin-sensitive Staphylococcus aureus (GMSSA). Seventeen of 29 patients with staphylococcal pneumonia were infected with GMRSA. Risk factors and associated diseases which selected for infection with GMRSA as opposed to GMSSA included prior antibiotic therapy for a prolonged period of time (p = 0.0001), number of risk factors per patient (p = 0.0001), days hospitalized prior to diagnosis of pneumonia (p = 0.002) and number of associated diseases per patient (p = 0.002). Despite the epidemiologic differences between GMSSA and GMRSA pneumonia, there were no differences in the clinical presentation, course of illness, complications, response to appropriate therapy or outcome between the two groups. Survival was adversely affected by age only among the GMSSA patients (p = 0.02) and by the number of associated diseases (p = 0.005).

Anti-Bacterial Agents↗
PubMed1980

Comparison of in vitro activity of Sch 21420, a gentamicin B derivative, with those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin.

Sch 21420 is a new aminoglycoside synthesized from gentamicin B. Susceptibility tests with Sch 21420, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin were performed on a variety of bacterial species including 44 with known mechanisms of resistance to aminoglycosides. Sch 21420 and amikacin had similar effects on all except Haemophilus influenzae and Neisseria species, which were more susceptible to amikacin. Except with some strains of Serratia marcescens, the drugs used were bactericidal. Sch 21420 and amikacin were more stable than the other four aminoglycosides in the presence of the inactivating enzymes produced by some strains. Strains which were very resistant to Sch 21420 and emikacin either were permeability mutants or produced AAC (6')-I inactivating enzyme. The effect of cations on the susceptibilities of these strains to Sch 21420 and amikacin was seen mostly with Pseudomonas aeruginosa and to Sch 21420 with Acinetobacter. Cations did not affect the susceptibilities of other Pseudomonas species, Enterobacteriaceae, Staphylococcus aureus, or Streptococcus faecalis to Sch 21420 or amikacin.

Amikacin↗
PubMed1973

Comparison of gentamicin, carbenicillin and gentamicin, and carbenicillin in Pseudomonas sepsis in monkeys.

Intravenous inoculation of 6.0 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intratracheal inoculation of 2.5 mg of vincristine sulfate resulted in fatal sepsis in all of three untreated control monkeys. After intramuscular administration of either 2.5 mg of gentamicin or 50 mg of carbenicillin per kg per day, three of four monkeys in each group survived. When both antibiotics were given at the same dose but in separate sites, six of eight monkeys survived. Antibacterial activity of serum from infected monkeys or normal monkeys was not appreciably different when the two antibiotics were combined. Under the conditions of this study, there was no apparent difference in response of monkeys treated either with gentamicin or carbenicillin alone or with the combination of the two antibiotics.

Animals↗
PubMed1989

Mobility of gentamicin resistance genes from staphylococci isolated in the United States: identification of Tn4031, a gentamicin resistance transposon from Staphylococcus epidermidis.

Homologous genes encoding resistance to gentamicin, tobramycin, and kanamycin through the bifunctional acetylating [AAC(6')] and phosphorylating [APH(2")] aminoglycoside-modifying enzyme were identified in staphylococci isolated from patients in the United States. The mobility of gentamicin resistance (Gmr) genes found on a prototype conjugative plasmid (pGO1) was compared with that of genes cloned from chromosomal sites. Plasmid-encoded Gmr genes and flanking sequences were introduced onto a temperature-sensitive plasmid (pRN3208) from pGO1 by homologous recombination between insertion sequence-like elements present on both replicons. Growth of Staphylococcus aureus strains containing the temperature-sensitive recombinant (pGO161) at the nonpermissive temperature for plasmid replication (42 degrees C) revealed no translocation of Gmr from its plasmid location. A transposon (Tn551) resident on the same replicon did translocate. Chromosomal Gmr determinants were cloned, together with the gene for trimethoprim resistance (dfrA), from three geographically distinct S. epidermidis isolates; two were subcloned onto temperature-sensitive Escherichia coli-S. aureus shuttle plasmids as 7.2-kilobase BglII fragments. Growth of both recombination-deficient and-proficient S. aureus strains containing the cloned genes at 42 degrees C allowed detection of transposition of Gmr sequences and identification of insertion into random chromosomal sites. We have designated this 5-kilobase transposon from S. epidermidis as Tn4031.

Cloning, Molecular↗
PubMed1988

[Clinical and fundamental studies on intravenous drip infusion of gentamicin in the pediatric field. Pediatric study group of gentamicin].

A multiclinic study of gentamicin (GM) given by intravenous drip infusion was carried out by the Gentamicin Pediatric Study Group. The results are summarized as follows: 1. Upon intravenous drip infusion of GM at a dose range of 2.0-2.5 mg/kg over a period of 0.5-1 hour, therapeutically effective serum concentrations of 4-12 micrograms/ml were obtained. These values are similar to reported values in previous studies using GM intramuscular injection. 2. High urinary concentrations were observed up to 6 hours after administration, and the urinary recovery rate was approximately 60%. 3. Of a total of 142 cases collected, 117 cases were evaluated. Efficacy rates by diseases were: 100% in pneumonia (30/30), 98.3% in urinary tract infections (59/60), and 92.3% in other infections (skin and soft tissue) (12/13), with an overall efficacy rate of 94.9% (including 77 "excellent" cases). 4. Bacteriological examinations showed high eradication rates with the use of GM; i.e., 80% with Staphylococcus aureus (8/10), 60% with Pseudomonas aeruginosa (3/5), 100% with Haemophilus influenzae (7/7) and 97.8% with Escherichia coli (44/45), achieving an overall eradication rate of 92.4%. In mixed infections, the eradication rate was 85.7% (6/7). 5. No ototoxicity, nephrotoxicity or allergic reactions was observed. Abnormal laboratory findings observed were: GOT elevation in 3.1% of cases, GPT elevation in 3.9%, platelet increase in 1.5% and eosinophil increase in 0.8%, thus an overall rate of the appearance of abnormality was 5.6%. The above results indicate that an intravenous drip infusion of GM is a useful method for treating infections in pediatrics.

Adolescent↗
PubMed1983

Comparison between the combination of azlocillin-gentamicin and ampicillin-gentamicin in the treatment of a nursery population.

Newborn, and particularly premature infants are prone to life-threatening infections. The combination of ampicillin-gentamicin (AM-G) has been used extensively in neonatal intensive care units (NICU). Because resistant bacteria emerged, a new drug--an acylureidopenicillin, azlocillin, with a wide antibacterial spectrum--has been developed. A prospective randomized study was performed in order to evaluate the combination of AM-G vs. azlocillin-gentamicin (AZ-G). Thirty neonates received AM-G and 28 received AZ-G. Definite infection was found in 15 AM-G patients and in 10 AZ-G patients. In these patients, the antibiotic regimen was changed in six of the AM-G and in one of the AZ-G patients. In each of the two treatment groups, one very-low-birth-weight baby died due to overwhelming sepsis. In vitro sensitivity to AZ-G was higher than to AM-G, according to azlocillin blood levels obtained. Infants weighting less than 2,350 g had lower clearance and volume of distribution than did infants weighing greater than 2,350 g. The serum half-life was approximately the same in both groups. It appears to be that in the NICU, the combination of AZ-G may be more effective than the AM-G combination.

Ampicillin↗
PubMed1982

Treatment of blepharitis and blepharoconjunctivitis: comparison of gentamicin-betamethasone, gentamicin alone and placebo.

At two university centres 46 patients presenting with symptomatic infective blepharitis or blepharoconjunctivitis participated in a double-blind study of a new antibiotic-steroid ointment containing gentamicin and betamethasone. There was no significant difference in response to 2 weeks of therapy between the patients treated with this ointment and those treated with either an ointment containing gentamicin alone or a placebo ointment. There was also no significant correlation between the clinical response and the results of the bacterial cultures of swabs obtained at the beginning and the end of the study. However, the patients treated with the placebo had a much higher rate of recurrence of their symptoms over a 6-week follow-up period. The patients who before treatment had associated rosacea, dry eyes and a long duration of symptoms showed a poor response to therapy.

Adolescent↗
PubMed1979

Prospective comparative evaluation of gentamicin or gentamicin plus cephalothin in the production of nephrotoxicity in man.

Recent studies in animal models have demonstrated that in contrast with humans, cephalothin (CTIN) does not increase gentamicin (GENT) nephrotoxicity, but rather protects against it, particularly when CTIN is given simultaneously with GENT. To investigate this phenomenon in humans a study was designed in which 67 patients suffering from mild infections were investigated. Thirty-three of them served as the control group receiving GENT alone at a dose of 1.5 mg/kg/8 hourly, while the remaining 34 received CTIN at a dose of 2 g or 3 g 8 hourly by i.v. bolus, either simultaneously with GENT or separated by a 4-h interval. Findings showed that: (a) cylindruria developed in 66.6% and 82.3% and 82.3% in the GENT and GENT + CTIN groups respectively, (b) urinary beta-glycuronidase activity increased in 57.5% and 75% (c) serum creatinine exceeded by 0.3 mg the initial values in 21.2% and 27.6% and (d) the blood urea was above 50 mg% in 18.1% and 17.6% of the patients. These results indicate that: (a) regardless of the route and order of administration simultaneous treatment did not protect against nephrotoxicity in humans; (b) the combination of GENTA plus CTIN has no synergistic effect on the production of elevated serum creatinine and rising blood urea; (c) urinary beta-glycuronidase is not a significant predictor of eventual nephrotoxicity; (d) the following risk factors influenced the appearance of nephrotoxicity in both groups: (1) elevated GENT trough levels greater than or equal to 2 mg/l; (2) a course of treatment longer than 10 days.

Adult↗
PubMed1992

Comparison of the gentamicin resistance transposon Tn5281 with regions encoding gentamicin resistance in Enterococcus faecalis isolates from diverse geographic locations.

The genetic determinant encoding gentamicin resistance (Gmr) on the beta-lactamase encoding plasmid pBEM10 of Enterococcus faecalis HH22 is carried on a transposon, termed Tn5281, that is highly related to the staphylococcal Gmr transposons Tn4001 found in Australian isolates of Staphylococcus aureus and Tn4031 found in United States isolates of Staphylococcus epidermidis. We have now studied plasmid DNA from Gmr strains of E. faecalis isolated from diverse geographical locations (Houston, Pennsylvania, Thailand, and Chile) by using restriction endonuclease analysis and DNA-DNA hybridization to determine whether other Gmr E. faecalis carry Tn5281 or a similar type of element. We also compared these enterococci to several United States isolates of Staphylococcus aureus with nonmobile Gmr determinants. Three E. faecalis isolates (from Houston and Chile) carried Tn5281-like elements, whereas two isolates (from Houston and Pennsylvania) had restriction endonuclease and DNA-DNA hybridization patterns more similar to those of the Tn4001-IS257 hybrid found in the nonmobile Gmr determinants in United States isolates of S. aureus. A strain from Thailand had a third pattern unrelated to either Tn5281 or the nonmobile Gmr determinants present in United States isolates of S. aureus. Our results demonstrate that there is both similarity and diversity between the Gmr determinant of strains of E. faecalis isolated in diverse geographic locations.

Anti-Bacterial Agents↗
PubMed2001

Therapeutic efficacy of liposome-encapsulated gentamicin in rat Klebsiella pneumoniae pneumonia in relation to impaired host defense and low bacterial susceptibility to gentamicin.

Long-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a single-dose study of immunocompetent rats with Klebsiella pneumoniae pneumonia. In the present study, the therapeutic efficacy of LE-GEN was evaluated by monitoring rat survival and bacterial counts in blood and lung tissue in clinically relevant models, addressing the issue of impaired host defense and low bacterial antibiotic susceptibility. The results show that in immunocompetent rats infected with the high-GEN-susceptibility K. pneumoniae strain, a single dose of LE-GEN is clearly superior to an equivalent dose of free GEN. Yet complete survival can also be obtained with multiple doses of free GEN. In leukopenic rats infected with the high-GEN-susceptible K. pneumoniae strain, free GEN at the maximum tolerated dose (MTD) was needed to obtain survival. However, with the addition of a single dose of LE-GEN to free-GEN treatment, complete survival can be obtained using a sevenfold-lower cumulative amount of GEN than with free-GEN treatment alone. In leukopenic rats infected with low-GEN-susceptible K. pneumoniae cells, free GEN at the MTD did not result in survival. The use of LE-GEN is needed for therapeutic success. Increasing LE-GEN bilayer fluidity resulted in an increased GEN release from the liposomes and hence improved rat survival, thus showing the importance of the liposome lipid composition for therapeutic efficacy. These results warrant further clinical studies of liposomal formulations of aminoglycosides in immunocompromised patients with severe infections.

Animals↗