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A corneal ulcer, infected with Pseudomonas aeruginosa and complicated by conjunctivitis and endophthalmitis, was treated successfully with systemic administration of ticarcillin and topical application of tobramycin. It is unlikely that carbenicillin, to which the organism was much less sensitive, would have attained sufficient tissue levels to control the infection.
The antibacterial activity of tobramycin, gentamicin, erythromycin, cloxacillin, kanamycin, cephalexin, penicillin, carbenicillin and polymyxin were compared against 303 clinical bacterial isolates from a pediatric hospital patient population. Standard disk diffusion and agar-dilution methods were employed. Significant activity was demonstrated for tobramycin against pseudomonas, Klebsiella, Escherichia coli and both Staphylococcus aureus and albus; Tobramycin was significantly more active against Pseudomonas than gentamicin or the other antibiotics testedmcomparable activity to gentamicin was present for the other types of bacteria; Cross-resistance was not encountered between tobramycin and gentamicin. 30 isolates of E. coli were tested against the combination of tobramycin and ampicillin by the growth-curve method. Synergism was demonstrated in 4 isolates, antagonism in 1 and an additive effect in 25. A bactericidal effect was present at 24h against 17 isolates with tobramycin alone and against 25 isolates when combined with ampicillin. These results provide in vitro rationale for the consideration of tobramycin for clinical use in patients with Psuedomonas infections for the combination of ampicillin and tobramycin for the treatment of selected E.coli infections.
The in vitro activity of gentamicin, tobramycin, sisomicin, netilmicin, amikacin, kanamycin and streptomycin was tested simultaneously by the agar dilution method against 584 clinical isolates of gram-negative bacilli that were resistant to gentamicin and/or tobramycin. About half of the gentamicin-resistant Pseudomonas were susceptible to tobramycin but cross-resistance was virtually complete between gentamicin and tobramycin for Enterobacteriaceae. Sisomicin was much more active than gentamicin against Klebsiella, Escherichia and Citrobacter species. Only 18.9%, 27.4% and 27.9% of Klebsiella, Enterobacter and Serratia respectively were resistant to netilmicin. Amikacin was the most effective aminoglycoside with an overall resistance of 15.6%. Kanamycin was effective against 40% of Proteus and Providencia species. Surprisingly, more than half of Klebsiella and Enterobacter species and 85.3% of Serratia species were susceptible to streptomycin.
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen, causing serious chronic infections. P. aeruginosa can adapt efficiently to antibiotic stressors via different genotypic or phenotypic strategies such as resistance and tolerance. The adaptation regulatory system is not always very well understood. In this study, we use shotgun proteomics to investigate the system-level response to tobramycin in two clinical wound P. aeruginosa isolates and PAO1. We profiled each strain for its antibiotic drug-tolerant phenotype using supra-minimum inhibitory concentrations (supra-MICs) of tobramycin and applied proteomics to investigate the protein expression profiles. The MIC revealed that all isolates were susceptible to tobramycin but at supra-MICs at stationary growth, a degree of tolerance was observed for the isolates. We identified around 40% of the total proteins encoded by the P. aeruginosa genome and highlighted shared and unique protein signatures for all isolates. Comparative proteome profiling in the absence of antibiotic treatment showed divergent fingerprints, despite similarities in the growth behavior of the isolates. In the presence of tobramycin, the isolates shared a common response in the downregulation of proteins involved in the two-component system, whereas stress response proteins were present at higher levels. Our findings provide insight into the use of proteomic tools to dissect the system-level response in clinical isolates in the absence and presence of antibiotic stress.
Tobramycin sulphate, a bactericidal aminoglycoside antibiotic, has been evaluated worldwide in 3,506 patients. Drug-related adverse effects were reported by the investigators in 3.9% of the cases, and included reactions in the nervous system (ototoxicity) in 0.6% and in the kidney in 1.5%. Effects of doubtful relationship to tobramycin occurred in 6.6% of the cases. The effects were usually reversible, although infrequently altered renal or eighth-nerve function appeared to persist in some of the patients. There were no deaths or instances of renal shutdown as a result of tobramycin therapy. Therefore, under the clinical conditions in which it was evaluated, tobramycin appeared to be well tolerated. The association of toxicity with various "risk factors" is discussed.
The case histories are described of two patients with normal renal function who developed permanent complete bilateral loss of peripheral vestibular function during tobramycin therapy. Despite the low incidence of the cochleotoxic and and vestibulotoxic side-effects of tobramycin, it seems advisable to monitor patients on tobramycin therapy for signs of vestibular dysfunction and hearing loss.
The cure rate of infections in cancer patients is adversely affected by neutropenia (less than 1,000/mm3). In particular, patients with severe neutropenia (less than 100/mm3) have shown a poor response to antibiotics. To overcome the adverse effects of neutropenia, tobramycin was given by continuous infusion and combined with intermittent carbenicillin. Tobramycin was given to a total daily dose of 300 mg/m2 and carbenicillin was given at a dose of 5 gm every four hours. There were 125 infectious episodes in 116 cancer patients receiving myelosuppressive chemotherapy. The overall cure rate was 70%. Pneumonia was the most common infection and 61% of 59 episodes were cured. Gram-negative bacilli were the most common causative organisms and 69% of these infections were cured. The most common pathogen was Klebsiella pneumoniae and this, together with Escherichia coli and Pseudomonas aeruginosa, accounted for 74% of all gram-negative bacillary infections. Response was not influenced by the initial neutrophil count, with a 62% cure rate for 39 episodes associated with severe neutropenia. However, failure of the neutrophil count to increase during therapy adversely affected response. Azotemia was the major side effect recognized, and it occurred in 11% of episodes. Major azotemia (serum creatinine greater than 2.5 mg/dl or BUN greater than 50 mg/dl) occurred in only 2%. Azotemia was not related to duration of therapy or serum tobramycin concentration. This antibiotic regimen showed both therapeutic efficacy and acceptable renal toxicity for these patients.
The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment.
Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.
In animal experiments the concentration of the antibiotic Tobramycin in the aqueous humor and blood serum following intramuscular and subconjunctival injections was tested by diffusion on agar plates. After intramuscular injections, only traces of Tobramycin were found in the aqueous humor, but a significantly higher concentration of the antibiotic was obtained by subconjunctival injections. The subconjunctival application of the antibiotic was well tolerated.
Tobramycin sulfate, an aminoglycoside antibiotic, has been shown to be effective in the treatment of complicated urinary tract infections. Because of this, a study was undertaken to determine the penetrance of tobramycin into the prostate gland. It was found that the drug is concentrated at inhibitory levels in the prostate gland after the routinely recommended administration and should be useful in the treatment of bacterial prostatic infection.
The effects of different concentrations of tobramycin, streptomycin, neomycin and gentamicin on the rat isolated phrenic nerve-diaphragm preparation are reported. Streptomycin, neomycin and gentamicin produced dose-dependent neuromuscular blockade. Tobramycin increased the muscle response at high concentrations (6.4 X 10(-4) - 2.6 X 10(-2) mol litre-1, but had no detectable effect when used in therapeutically recommended concentrations.
Isolates from the blood of 30 patients with endocarditis due to Pseudomonas aeruginosa were tested for synergy between carbenicillin and an aminoglycoside, either gentamicin or tobramycin, by in vitro checkerboard methods in modified (cation-supplemented) Mueller-Hinton broth. Twenty-five of the 30 isolates were affected synergistically. Whether given low (2.5--5 mg/kg) or high (8 mg/kg) doses of aminoglycoside along with 30 g of carbenicillin daily, all of the five patients infected with pseudomonads that were not synergistically affected were refractory to treatment with pseudomonads that were not synergistically affected were refractory to treatment with the carbenicillin-gentamicin combination, whereas the finding of synergy of carbenicillin with gentamicin (or tobramycin) did not assure a medical cure. Tests for synergy between carbenicillin and gentamicin yielded different results in Mueller-Hinton agar than in modified Mueller-Hinton broth. The majority (28) of 30 isolates of endocarditis-producing P. aeruginosa were resistant to the bactericidal effects of 50% pooled normal serum that had been freshly separated. One of the endocarditis-producing strains that was sensitive to 50% serum was resistant to 10% serum. However, sensitivity or resistance to freshly separated, pooled normal human serum did not predict the outcome of antibacterial therapy for pseudomonas endocarditis.
Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.
Of 97 well-defined strains of Pseudomonas, isolated from sputum of patients with cystic fibrosis (CF), the minimum inhibitory concentration (MIC) of several antibiotics was determined with a broth dilution method. The majority of the strains were resistant to ampicillin and cephalothin, moderately susceptible to carbenicillin (70% to 100 microgram/ml) and highly susceptible to piperacillin (100% to 25 microgram/ml, 88% to 6.25 microgram and 60% to 3.12 microgram/ml). If the pharmacological properties of piperacillin are comparable with those of carbenicillin, it can be expected that the sputum level of this drug will be adequate to treat Pseudomonas pulmonary infections. At the lowest concentration tested (0.78 microgram/ml) 3% of the strains were susceptible to kanamycin, 85,5% to amikacin, 95% to gentamicin, 98% of tobramycin, and 80% to colimycin. With regard to clinically attainable concentrations, 98.9% of the strains were susceptible to gentamicin and tobramycin 97.9% to amikacin, 96.9% to colimycin, 88.6% to piperacillin, 38% to carbenicillin, 25.7% to kanamycin, 12.3% to ampicillin, and 1% to cephalothin.
6,042 strains of Staphylococcus aureus, Streptococcus faecalis, Proteus mirabilis, Escherichia coli, Klebsiella sp. and Pseudomonas sp. were tested against tobramycin and gentamicin. Among all species studies, except Pseudomonas sp, gentamicin turned out to be slightly superior to tobramycin.
The authors have studied on 20 bacterial strains (5 Pseudomonas aeruginosa, 5 Escherichia coli, 5 Klebsiella and 5 Serratia) the bactericidal kinetics of 4 aminoglycoside antibiotics: amikacin, gentamicin, kanamycin and tobramycin. The antibiotic concentrations used for this work were 1.5 times the MIC for each strain previously measured in a liquid medium. The action of the aminoglycoside antibiotics shows three phases. The third phase describes a part of less susceptible bacterial population. It permits the comparison of the 4 antibiotics. Amikacin shows the best activity, followed by gentamicin, kanamycin and tobramycin.
Twenty-five isolates of Staphylococcus aureus, 24 isolates of Escherichia coli, and 25 isolates of Klebsiella pneumoniae obtained from clinical material were tested in vitro for susceptibility to cefamandole, tobramycin and combinations of the two antibiotics utilizing an automated microdilution system. Synergistic or partially synergistic bactericidal effects of the combination were observed against 15 of the S. aureus isolates (60%), 23 of the E. coli isolates (96%), and 19 of the K. pneumoniae isolates (76%) tested. No antagonistic effects of the combination were noted. This study suggests that cefamandole-tobramycin combinations are capable of acting synergistically in vitro against certain gram-positive and gram-negative organisms and may have potential usefulness in clinical situations such as gram-negative rod and staphylococcal sepsis.