In vitro acitivity of sisomicin, an aminoglycoside antibiotic, against clinical isolates.

The in vitro activity of the aminoglycoside antibiotics tobramycin, sisomicin, amikacin, gentamicin, and netilmicin (SCH 20569) were compared against 26 gentamicin-resistant isolates of Pseudomonas aeruginosa cultured from hospitalized children. Tobramycin had the greatest activity on a weight basis, followed by sisomicin, gentamicin, amikacin, and netilmicin. All isolates were resistant to achievable concentrations of netilmicin and gentamicin, but 23% were inhibited by achievable concentrations of tobramycin, 8% by amikacin, and 4% by sisomicin. The combinations carbenicillin/tobramycin, carbenicillin/sisomicin, and carbenicillin/amikacin were synergistic for 92% of strains; antagonism was not encountered. These in vitro results suggest that tobramycin, sisomicin, or amikacin in combination with carbenicillin would be the safest initial regimen in the therapy of gentamicin-resistant Pseudomonas infections pending susceptibility studies.Pseudomonas aeruginosa resistant to currently available antibiotics, including gentamicin, are becoming more prevalent. A study was undertaken to investigate the activity of several new aminoglycosides against a population of gentamicin-resistant P. aeruginosa to determine the extent of cross-resistance between tobramycin, sisomicin, amikacin, netilmicin (SCH 20569), and gentamicin. The possibility of carbenicillin/aminoglycoside synergism against this resistant population of P. aeruginosa was also examined. MATERIALS AND METHODSTwenty-six strains of P. aeruginosa were isolated from 23 patients at the Montreal Children's Hospital and identified by using standard microbiological techniques. At least 14 different types ofPseudomonas were represented among the isolates studied, as determined by serological and phage-typing methods (kindly performed by N. Hinton, Toronto). All strains were screened for resistance to gentamicin by a standardized disk diffusion test (16) and were considered resistant if the zone diameter was <13 mm and the agar dilution minimum inhibitory concentration (MIC) was -6.25 lAg/ml. Bacteria were stored in sheep blood at -20°C until tested.Tobramycin sulfate was supplied as a solution of 1,000 ,ig/ml and was stored at 4°C. Gentamicin, sisomicin, amikacin, netilmicin, and carbenicillin were supplied as dry powders and were reconstituted immediately before use. Agar dilution MICs were performed according to the method of Steers et al. (19) using Mueller-Hinton agar (Ca2+, 7 mg/100 ml, Mg2+, 3.6 mg/100 ml) and an inoculum of 106 to 107 bacteria/ml. The MIC was defined as the lowest concentration of drug allowing no colonial growth on the surface of the agar.Plates for single antibiotic agar dilution studies were prepared 48 h in advance and stored at 4°C. Plates for combination studies were prepared 2 h before use. Synergism was tested by adding either 25 or 50 ,ug of carbenicillin per ml to each dilution of four of the aminoglycosides listed above. The combination was considered synergistic if there was a decrease of four double dilutions or greater in the ami...

Section: Resultsmentioning

confidence: 99%

Activity of Newer Aminoglycosides and Carbenicillin, Alone and in Combination, Against Gentamicin-Resistant Pseudomonas aeruginosa

Marks

Hammerberg

Greenstone

et al. 1976

“…In vitro studies support the use of this agent for the treatment of selected infections due to gentamicin-resistant bacteria (4,6,9,14). Preliminary in vitro studies in our laboratory indicated activity for sisomicin against some gentamicin-resistant P. aeruginosa as well as synergism between carbenicillin and sisomicin (5,6).…”

Section: Discussionmentioning

confidence: 88%

“…Sisomicin is a new aminoglycoside antibiotic derived from the fermentation broth of Micromonospora inyoenis that has many properties in common with gentamicin as well as the advantage of activity against selected gentamicinresistant bacteria (4,6,9,14). The purpose of this study was to examine some of the pharmacokinetic, clinical, and toxicological properties of sisomicin in the therapy of serious infections of children.…”

mentioning

confidence: 99%

Clinico-Pharmacological Studies of Sisomicin in Ill Children

Marks

Vose

Hammerberg

et al. 1978

Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 ,g/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 isg/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval.The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.The emergence of gentamicin-resistant bacteria in hospitalized patients has emphasized the importance of evaluating alternative antibiotics. Sisomicin is a new aminoglycoside antibiotic derived from the fermentation broth of Micromonospora inyoenis that has many properties in common with gentamicin as well as the advantage of activity against selected gentamicinresistant bacteria (4,6,9,14). The purpose of this study was to examine some of the pharmacokinetic, clinical, and toxicological properties of sisomicin in the therapy of serious infections of children. MATERIALS AND METHODSSisomicin was administered to 12 patients hospitalized at the Montreal Children's Hospital. These patients were selected by the attending physician as candidates for aminoglycoside therapy using standard clinical and laboratory criteria. Once a patient was selected to receive aminoglycosides, sisomicin was offered in lieu of gentamicin after carefully explaining the nature of the study and the differences between the two drugs to the parents and only after obtaining informed consent. Appropriate bacterial cultures and base-line laboratory studies were obtained in each case. When positive cultures were obtained before therapy, appropriate cultures were repeated during and after therapy as well. Sisomicin was administered in a dosage of4.5 mg/kg per day intravenously (divided every 8 h) over 0.5 h, and the duration of treatment was determined by standard clinical and bacteriological criteria.All patients were carefully examined for tolerance to the drug and for hematological, hepatic, and renal toxicities by the following tests: hemoglobin, hematocrit, white blood count and differential, platelets, serum glutamic oxaloacetic transa inase, bilirubin, alkaline phosphatase; urea nitrogen, creatinine, and urinalysis. These tests were carried out before, during, and after therapy.Audiological evaluations were performed within 72 h of initiation of therapy, and again after completion of the course of sisomicin. School-age children were studied by standard pure-tone and standard speech audiometry and impedance testing, pre-school children and infants by behavioral observation, play, and conditioned orienting response audiometry, and impedance measurements when...

“…Over 80% of clinical isolates of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., and Proteus spp. are inhibited by a concentration of 0.78 ,g/ml or less in vitro (10). Pharmacological studies in humans have shown that a dose of 30 mg/M2 administered intravenously over 0.5 h results in a mean peak serum concentration of about 5 ,ug/ml, with a mean serum concentration of 1 jig/ml at the end of 4 h (7).…”

mentioning

confidence: 99%

“…Tagit (0.2 ,ug) was dissolved in benzene and evaporated under nitrogen to dryness. The following reagents were added to the residue within 1 min: 1 mCi of high-specific-activity (100 mCi/ml) carrier-free 125I (Amersham/Searle, Des Plaines, Ill.), chloramine-T (50 ,ug in 10 pl of 0.2 M phosphate buffer, pH 7.5), sodium metabisulfite (120 Ag in 10 ,ul of phosphate buffer. pH 7.5), potassium iodide (200 ,g in 10 p1l of 0.2 M phosphate buffer, pH 7.5), and dimethylformamide (10 .ld).…”

mentioning

confidence: 99%

Radioimmunoassay of Sisomicin

Broughton

Strong²,

Bodey³

1976

Self Cite

An antibody induced in rabbits against a gentamicin-bovine serum albumin conjugate cross-reacted with the chemically related aminoglycoside, sisomicin, facilitating the development of a sisomicin radioimmunoassay. Sisomicin was labeled with 12'5 using an acylating agent [3-(4-hydroxyphenyl)propionic acid-N-hydroxy-succinimide ester]. The resulting assay produced a linear standard curve on a logit-log plot with a sensitivity of 140 pg. Comparison with a microbiological assay showed no significant difference (P < 0.001) in the measurement of sisomicin by these two methods.