Antimicrobial Effectiveness of Kanamycin, Aminosidin, B8-K8, Sisomicin, Gentamicin and Tobramycin Combined with Carbenicillin or Cephalothin Against Gram-Negative Rods

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: Resultssupporting

confidence: 79%

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

Marks

Hammerberg

Greenstone

et al. 1976

“…This combination is synergistic in vitro against Pseudomonas (1,6). In 1971, McLaughlin and Reeves (7) demonstrated that gentamicin can be inactivated by carbenicillin in vitro.…”

mentioning

confidence: 99%

Animal model distinguishing in vitro from in vivo carbenicillin-aminoglycoside interactions

Pieper¹,

Vidal²,

Schentag³

1980

Aminoglycosides and carbenicillin are frequently co-administered to patients with serious gram-negative infections. Aminoglycosides are inactivated by carbenicillin in vitro, and a loss of antibacterial activity of both antibiotics results. Although these interactions are presumed to occur in vivo, previous studies have not used assay methodology that can distinguish inactivation occurring prior to and during microbiological assay from inactivation in vivo. To address this problem, we gave seven bilaterally nephrectomized mongrel dogs doses designed to achieve simultaneous therapeutic serum concentrations of aminoglycosides and carbenicillin. Serum samples were tested by radioimmunoassay on three occasions: immediately, to determine in vivo interactions, and at 24 h and 1 week to assess the time course of in vitro inactivation. In comparison with immediate radioimmunoassay, gentamicin and tobramycin concentrations decreased by 39 and 53%, respectively, when assayed at 24 h (P < 0.05) and by 75 and 82% when assayed at 7 days (P < 0.001). In contrast, amikacin concentrations were reduced by only 9 and 30% at 24 h and 7 days. Tobramycin concentrations were also determined by immediate microbiological assay and were found to be similar to those in samples stored for 24 h before radioimmunoassay. Immediate radioimmunoassay demonstrated that carbenicillin reduced in vivo serum half-lives of gentamicin and tobramycin by 40% (P < 0.05). The half-life of amikacin in vivo was not significantly altered. In the presence of carbenicillin, amikacin was the most stable aminoglycoside both in vivo and in vitro, and it is the aminoglycoside of choice in patients with renal failure who require this combination.

“…van Eys, Cancer, in press). The combination of carbenicillin or ticarcillin with an aminoglycoside provides a broad spectrum of activity against gram-negative bacilli and has been shown to be synergistic against Pseudomonas aeruginosa and various Enterobacteriaceae (1,2,6,11,13,17). Conversely, inactivation of aminoglycoside antibiotics has been shown to be caused by either ticarcillin or carbenicillin (7,10,15,16,18,21).…”

mentioning

confidence: 99%

Effect of Time and Concentration Upon Interaction Between Gentamicin, Tobramycin, Netilmicin, or Amikacin and Carbenicillin or Ticarcillin

Pickering

Gearhart

1979

An aminoglycoside antibiotic and carbenicillin or ticarcillin are widely used in the treatment of patients with gram-negative bacillus infections. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycosides at two concentrations with carbenicillin or ticarcillin at four concentrations. By linear regression analysis, the inactivation of each aminoglycoside was shown to be directly proportional to the concentration of carbenicillin ( P < 0.001). Inactivation was significantly ( P < 0.01) greater for gentamicin and tobramycin than for amikacin or netilmicin at all carbenicillin concentrations. At carbenicillin concentrations of 300 and 600 μg/ml, significantly ( P < 0.005) less inactivation of amikacin occurred when compared to netilmicin. Ticarcillin produced a significant ( P < 0.025) inactivation of gentamicin and tobramycin, with inactivation being directly proportional to ticarcillin concentration. No inactivation of amikacin or netilmicin activity occurred unless the ticarcillin concentration was 600 μg/ml. No significant change in aminoglycoside activity occurred when stored with ticarcillin or carbenicillin at concentrations ranging from 100 to 600 μg/ml at −70°C for 56 days. When an aminoglycoside and carbenicillin or ticarcillin are indicated in patients with renal failure, this study supports the use of ticarcillin with either amikacin or netilmicin.