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At least 19 recordsLinked to original sources
PubMed1998

A clinical evaluation of diclofenac-gentamicin combination eye drops in the control of inflammation after cataract surgery. Diclofenac-Gentamicin versus Gentamicin Study Group.

The purpose of this study was to compare the efficacy and safety of diclofenac-gentamicin (DR 1352/1) combination eye drops with gentamicin eye drops in the postoperative management of patients undergoing extracapsular cataract surgery and lens implantation. This was a prospective, randomised, double-masked, parallel-group, four-week, multicentre study with patient visits preoperatively, on the day of surgery, and postoperatively on days 1, 5-8, 12-16, and 26-32. Of the 196 patients (diclofenac-gentamicin 99, gentamicin 97) recruited into the study, 161 (diclofenac-gentamicin 83, gentamicin 78) were available for per-protocol analyses. The two treatment groups were clinically similar at baseline. On days 12-16 postoperatively, diclofenac-gentamicin was significantly more effective (p = 0.002) than gentamicin in reducing intraocular inflammation as assessed by the sum of grades of anterior chamber cells and flare. The level of conjunctival hyperaemia was significantly less in the diclofenac-gentamicin group compared with the gentamicin group on postoperative days 5-8 and 12-16. There was no significant difference between the two study groups in the global assessment of local tolerance. Possibly drug-related adverse events were slightly more in the diclofenac-gentamicin group (22,22%) compared with gentamicin (17,17%); however, all affected study patients normalised with appropriate therapy except one patient with endophthalmitis. In conclusion, diclofenac-gentamicin (DR1352/1) eye drops were more effective than gentamicin eye drops and appeared to be as safe in the control of post-cataract surgery inflammation.

Aged↗
PubMed1984

Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

The divalent cations, Ca++ and Mg++, are known to competitively inhibit a large number of aminoglycoside-membrane interactions, so that Ca++ prevents both the neurotoxic and ototoxic effects of these antibiotics acutely in vitro. Since gentamicin-induced plasma and subcellular membrane damage appear to be critical pathogenetic events in gentamicin nephrotoxicity, Ca++ may play a similar protective role in gentamicin-induced acute renal failure. To test this possibility in vivo, rats (group 2) were given a 4% calcium (in the form of CaCO3) supplemented diet to increase delivery of Ca++ to the kidney and administered single daily subcutaneous injections of gentamicin, 100 mg/kg, for 10 d. Compared with a simultaneously studied group (group 1) of rats receiving identical gentamicin dosages and normal diets, Ca++ supplementation ameliorated gentamicin-induced acute renal failure. After 10 doses of gentamicin, blood-urea nitrogen values in group 1 averaged 213 +/- 15 (SE) and 25 +/- 3 (P less than 0.001) in group 2. The progressive decline in renal excretory function, as measured by BUN, in group 1 animals was accompanied by simultaneous declines in renal cortical mitochondrial function and elevations in renal cortex and mitochondrial Ca++ content, quantitative indices of the degree of renal tubular cell injury. Oral Ca++ loading markedly attenuated these gentamicin-induced derangements. After eight and 10 doses of gentamicin, mitochondria isolated from the renal cortex of group 2 rats had significantly higher rates of respiration supported by pyruvate-malate, succinate and N,N,N',N'-tetramethyl-p-phenyldiamine-ascorbate, higher rates of dinitrophenol-uncoupled respiration and greater acceptor control ratios than those measured in mitochondria isolated from the renal cortex of group 1 animals. Similarly, after 8 and 10 doses, renal cortex and renal cortical mitochondrial Ca++ content of group 2 was significantly lower than values observed in group 1. Thus, dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamicin-induced acute renal failure. The mechanism for this protective effect of Ca++ may relate to the manner in which this polycationic antibiotic interacts with anionic sites, primarily the acidic phospholipids of renal membranes. In this regard, Ca++ was found to be a competitive inhibitor both of 125I-gentamicin binding to renal brush border membranes, the initial site of interaction between gentamicin and renal proximal tubule cells, with a composite inhibition constant (Ki) of 12 mM and of 125I-gentamicin binding to phosphatidic acid, an important membrane acidic phosph

Acute Kidney Injury↗
PubMed1998

A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate.

PURPOSE: The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels. RESULTS: Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.

Adult↗
PubMed2000

Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses.

OBJECTIVE: To compare concentrations of gentamicin in serum and bronchial lavage fluid after IV and aerosol administration of gentamicin to horses. ANIMALS: 9 healthy adult horses. PROCEDURE: Gentamicin was administered by aerosolization (20 ml of gentamicin solution [50 mg/ml]) and IV injection (6.6 mg of gentamicin/kg of body weight) to each horse, with a minimum of 2 weeks between treatments. Samples of pulmonary epithelial lining fluid were collected by small volume (30 ml) bronchial lavage 0.5, 4, 8, and 24 hours after gentamicin administration. Serum samples were obtained at the same times. All samples were analyzed for gentamicin concentration, and cytologic examinations were performed on aliquots of bronchial lavage fluid collected at 0.5, 8, and 24 hours. RESULTS: Gentamicin concentrations in bronchial lavage fluid were significantly greater 0.5, 4, and 8 hours after aerosol administration, whereas serum concentrations were significantly less at all times after aerosol administration, compared with IV administration. Neutrophil counts in bronchial lavage fluid increased from 0.5 to 24 hours, regardless of route of gentamicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Aerosol administration of gentamicin to healthy horses resulted in gentamicin concentrations in bronchial fluid that were significantly greater than those obtained after IV administration. A mild inflammatory cell response was associated with aerosol delivery of gentamicin and repeated bronchial lavage. Aerosol administration of gentamicin may have clinical use in the treatment of bacterial bronchopneumonia in horses.

Administration, Inhalation↗
PubMed1988

Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats.

Hematologic and serum biochemical values, tissue gentamicin concentrations, and renal pathologic changes were determined in clinically normal and endotoxemic cats given 3 mg of gentamicin/kg of body weight, IV. Endotoxemia was induced by IV administration of 0.5 microgram of Escherichia coli endotoxin/kg of body weight. In experiment 1, 6 cats were given endotoxin. After rectal temperature increased at least 1 degree C, cats were given gentamicin. Blood samples were collected before and at 1 and 3 hours after administration of gentamicin. With the exception of severe leukopenia, other hematologic changes or changes in serum biochemical values were not observed. In experiment 2, 24 cats were allotted to 4 groups and were given gentamicin, endotoxin, gentamicin plus endotoxin, or neither substance. Three hours later, cats were euthanatized, and tissue and body fluid specimens were obtained and were assayed for gentamicin concentration. Kidney specimens were examined microscopically. Endotoxemic cats had more gentamicin in the renal medulla than did control cats, but none of the cats had detectable renal lesions. The possible nephrotoxic synergism between gentamicin and severe endotoxemia and the lack of major differences in gentamicin concentration in extrarenal tissues indicated that the dosage of gentamicin in endotoxemic cats does not have to exceed the dosage recommended for clinically normal cats. A single dose of gentamicin administered IV did not cause renal damage in mildly endotoxemic cats, but nephrotoxicity ascribed to multiple doses of gentamicin in more severely endotoxemic cats needs to be evaluated.

Animals↗
PubMed1995

Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin.

This study compares the effects of a total daily dose of gentamicin given once a day (q.d.) or three times a day (t.i.d.) in the therapy of experimental endocarditis in rabbits caused by penicillin-susceptible, penicillin-tolerant, or penicillin-resistant viridans streptococci. Four isolates were used in vivo: one penicillin susceptible (MIC < or = 0.03 microgram/ml), one penicillin tolerant (MBC/MIC, < or = 0.03/ > 32 micrograms/ml), and two penicillin resistant (MICs = 0.5 and 2 micrograms/ml). Animals were infected with one of the four isolates and assigned to one of the following treatment regimens: no treatment, procaine penicillin at 1.2 million IU intramuscularly (i.m.) t.i.d., procaine penicillin plus gentamicin at 1 mg/kg of body weight i.m. t.i.d., procaine penicillin plus gentamicin at 3 mg/kg i.m. q.d., or procaine penicillin plus gentamicin at 1 mg/kg i.m. q.d. (only animals infected with the penicillin-susceptible isolate). Serum drug concentrations measured 30 min after administration of 1.2 million IU of penicillin and 1 or 3 mg of gentamicin per kg were 22.6, 3.8, and 8.5 micrograms/ml, respectively. The reduced total daily dose of gentamicin was ineffective among animals infected with penicillin-susceptible viridans streptococci; treatment with 1 mg of gentamicin per kg per day plus penicillin was less effective (P < 0.05) than was treatment with 3 mg of gentamicin per kg per day plus penicillin. The 1-mg/kg/day gentamicin treatment regimen was not further studied. The gentamicin dosing interval did not significantly affect (q.d. versus t.i.d., P > 0.05) the relative efficacy of penicillin plus gentamicin for treatment of experimental endocarditis among animals infected with each of the four isolates tested.

Animals↗
PubMed1988

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin.

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Prolonged persistence on the ocular surface of fortified gentamicin ointment as compared to fortified gentamicin eye drops.

PURPOSE: A comparative study on the elimination of gentamicin from the ocular surface and the concentration of gentamicin in the anterior chamber following application of either an ointment or eye drops containing equal concentrations (1.5%) of gentamicin. METHODS: A disc-diffusion test was used to determine the concentration of gentamicin in fornix inferior of 10 persons. The anterior chamber concentration of gentamicin was determined in 5 cataract patients by the TDX analyzer, Abbot Laboratories, II., USA. RESULTS: Ten minutes following application, the concentration of gentamicin was significantly higher in the eyes receiving ointment (310.6 mg/L) compared to drops (45 mg/L) (p<0.01). Furthermore, gentamicin could be detected 40 minutes after application in the eyes receiving ointment compared to 10 minutes in the eyes receiving drops. The anterior chamber concentration of gentamicin after application of either drops or ointment was lower than 0.6 mg/L and thus below detection limit. CONCLUSIONS: The persistence of gentamicin ointment was significantly longer on the ocular surface as compared to gentamicin eye drops. Gentamycin ointment may thus provide a means to reduce the high application frequency presently in use with eye drops to treat bacterial keratitis and thereby reduce patient inconvenience, especially during nighttime.

Adult↗
PubMed1996

Vancomycin-gentamicin synergism revisited: effect of gentamicin susceptibility of methicillin-resistant Staphylococcus aureus.

Vancomycin monotherapy of deep-seated staphylococcal infection may be associated with poor bacteriological response. We evaluated 24 unique patient isolates of methicillin-resistant Staphylococcus aureus (MRSA) for vancomycin-gentamicin synergism by determining time-kill curves for vancomycin at 10 micrograms/ml and gentamicin at 1 microgram/ml. Nine MRSA strains showed high-level gentamicin resistance (HLGR) (MIC, > 500 micrograms/ml), and 15 did not. Vancomycin-gentamicin demonstrated synergism against none of the HLGR strains. For the non-HLGR strains, gentamicin agar dilution MICs ranged from 0.5 to > 128 micrograms/ml. Vancomycin-gentamicin demonstrated synergism against six of these strains and indifference against nine of them. There was no relationship between the agar dilution MIC of gentamicin and the occurrence of synergism against non-HLGR strains. We conclude that a gentamicin MIC of > 500 micrograms/ml predicts a lack of vancomycin-gentamicin synergism for strains of MRSA. For non-HLGR strains, synergism is not predictable from the gentamicin MIC.

Drug Synergism↗
PubMed2003

The effect of vecuronium is enhanced by a large rather than a modest dose of gentamicin as compared with no preoperative gentamicin.

UNLABELLED: We compared the effect of two doses of gentamicin versus no gentamicin (NG) given before surgery on the neuromuscular relaxant effect of vecuronium. Seventy patients (intraabdominal procedures) were randomly allocated to receive preoperative large-dose (4 mg/kg) gentamicin (LD), a modest dose (1.2 mg/kg) of gentamicin (MD), or NG. No more than one dose of gentamicin was given before the vecuronium administration. Serum gentamicin levels, the time for 25% recovery of the first twitch in the train-of-four after a bolus of vecuronium, and the time from cessation of the vecuronium infusion to extubation of the trachea were estimated. Serum gentamicin levels were higher (P < 0.001) for LD than MD. The time for 25% recovery of the first twitch after the vecuronium bolus was slightly longer with LD than MD (P = 0.06) and longer in LD than NG (P = 0.001) (42.9 +/- 23.6 min versus 36.2 +/- 17 min and 27.4 +/- 9 min, respectively). The time to extubation was similar with LD and MD and longer for LD than NG (P = 0.008) (34.7 +/- 19.2 min versus 27.4 +/- 19.3 min and 19.4 +/- 10.1 min, respectively). The differences in these times were insignificant between MD and NG. Gentamicin administered as a LD rather than MD enhanced the neuromuscular blockade of vecuronium as compared with NG given before surgery. IMPLICATIONS: We demonstrated that the neuromuscular relaxant effect of vecuronium is enhanced by a large (4 mg/kg) rather than a modest (1.2 mg/kg) dose of gentamicin as compared with no gentamicin given before surgery.

Aged↗
PubMed2006

Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints of horses after implantation of gentamicin-impregnated collagen sponges.

OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6 healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically. RESULTS: Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range, 115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage.

Animals↗
PubMed1987

Gentamicin resistance among gram-negative bacillary blood isolates in a hospital with long-term use of gentamicin.

Between 1977 and 1985, gentamicin was the only formulary aminoglycoside at the Buffalo Veterans Administration Medical Center. During this time, there was a significant increase in the amount of gentamicin purchased. Amikacin represented 11% or less of the total aminoglycoside purchased in the same period, but purchases of this agent also significantly increased. Because of this long-term use of gentamicin, a retrospective analysis of gentamicin resistance among gram-negative bacillary blood isolates was performed. The results of this review revealed no significant change in the overall incidence of gram-negative bacteremia; approximately 75% of these bacteremic episodes were hospital acquired. The mean yearly gentamicin-resistance rate of gram-negative blood isolates was 13.2% (range, 6% to 18%) with no significant change in the rate for the period reviewed. However, for certain strains there were fluctuations in the percentage of resistance from year to year, suggesting that clusters of infections due to these organisms had occurred. Bacteremic infection due to resistant organisms was a major contributor to the overall level of gentamicin resistance among blood isolates. Amikacin resistance among gram-negative blood isolates was rare. In conclusion, despite the predominant use of gentamicin there was no change in the gentamicin resistance rate among gram-negative bacillary blood isolates during a nine-year period. The rate of gentamicin resistance among blood isolates appeared to be related to outbreaks/clusters of infections due to resistant strains rather than the frequency of use of gentamicin.

Amikacin↗
PubMed1982

Piperacillin and gentamicin v carbenicillin and gentamicin for treatment of serious gram-negative infections.

Piperacillin sodium, a new penicillin with remarkable in vitro activity against Pseudomonas aeruginosa and other Gram-negative bacilli, and gentamicin sulfate were compared with carbenicillin disodium and gentamicin in a prospective, randomized, double-blind comparison for treating serious Gram-negative infections. Of the 32 patients whose courses were "evaluable" for efficacy, 12 of 14 who received piperacillin and gentamicin and 13 of 18 who received carbenicillin and gentamicin had favorable outcomes. Of the 99 patients whose courses were evaluable for toxicity, nine of 51 recipients of piperacillin and gentamicin and 15 of 48 recipients of carbenicillin and gentamicin suffered clinical reactions possibly, probably, or definitely related to the penicillin. No statistically significant differences were found in the two groups in the frequencies of biochemical abnormalities, including hypokalemia, that occurred in 19 or 44 recipients of piperacillin and gentamicin and 16 of 45 recipients of carbenicillin and gentamicin. Thus, this study did not prove differences in efficacy of toxicity for piperacillin and gentamicin plus carbenicillin and gentamicin for serious Gram-negative infections.

Bacterial Infections↗
PubMed2005

Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats.

INTRODUCTION: In spite of new surgical techniques and recently developed antibiotics, there is no satisfactory solution for the treatment of chronic posttraumatic osteomyelitis. The introduction of local antibiotic treatment with gentamicin-PMMA beads according to Klemm has provided new stimuli for the treatment of chronic osteomyelitis. With the development of collagen as an absorbable carrier substance, the disadvantages of the rigid carrier system became evident. Due to the varying surgical techniques and different forms of adjuvant therapy, it is difficult to assess therapeutic methods and compare different studies. Therefore, it seemed appropriate to study the effect of local treatment with different antibiotic carriers in the setting of an animal study. MATERIALS AND METHODS: The proven rat model for Staphylococcus aureus-induced osteomyelitis was used to compare the results of monotherapy with cefazolin, gentamicin-PMMA beads, or gentamicin-containing collagen sponge with the combination of local and systemic antibiotic treatment. RESULTS: Single-agent therapy with parenterally administered cefazolin reduced the CFU from 3.7 x 10(6) to 2.9 x 10(4) g(-1) of tibial bone. The effect on osteomyelitis was more pronounced with the local application of antibiotics. The best results were achieved with the gentamicin-containing collagen sponge which reduced the bacterial colony count to 1.4 x 10(2) CFU/g compared with 9.8 x 10(2) CFU/g achieved with gentamicin-PMMA beads. The effect was most marked using a 4-week combination therapy with local application of the gentamicin-containing collagen sponge and systemic administration of cefazolin. In 9 of 11 animals, no bacteria could be detected in the bone. CONCLUSION: Each of the treatment modalities resulted in a significant therapeutic effect. Due to its ability to quickly release large amounts of gentamicin, the flexible gentamicin-containing collagen sponge proved to be superior to the rigid PMMA system. Although the gentamicin-containing collagen sponge provided high antibiotic concentration at the site of implantation, an additive effect was attained when combined with systemic antibiotic treatment.

Animals↗
PubMed1999

Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: a phenotypic assessment of NCCLS guidelines.

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 micrograms/mL and 2000 micrograms/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC < or = 500 micrograms/mL (n = 3,132; 71%); a MIC > 500, but < or = 2000 micrograms/mL (n = 441; 10%); and those with a MIC > 2000 micrograms/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin. Testing was done by a time-kill method using clinically achievable levels of ampicillin and gentamicin. We found that for the gentamicin MIC < or = 500 micrograms/mL group, 7 of 10 isolates demonstrated synergy with ampicillin as manifested by a > or = 2 log10 increase in killing versus the effect of ampicillin alone (at 1/2 the MIC for ampicillin). In the group sensitive to a gentamicin MIC range between > 500 and < or = 2,000 micrograms/mL, none of the 10 isolates demonstrated synergy. Absence of synergy was also found in the group resistant to 2,000 micrograms/mL of gentamicin. Assessment of eight additional enterococcal isolates with reduced sensitivity to ampicillin (MIC from 32-256 micrograms/mL) found no correlation between gentamicin sensitivity at 500 micrograms/mL and any in vitro test for synergy, nor with clinical therapeutic outcome. Gentamicin at 2 micrograms/mL combined with ampicillin was as effective in enhancing killing as a higher level of 4 micrograms/mL. These findings validate the current NCCLS guideline for predicting synergistic activity against enterococci in strains with usual susceptibility to ampicillin, and suggest that a therapeutic level less than maximal recommended dosing is sufficient when using gentamicin in this setting.

Ampicillin↗
PubMed1976

Emergence of gentamicin-resistant bacteria: experience with tobramycin therapy of infections due to gentamicin-resistant organisms.

A computerized system for testing and surveillance of bacterial susceptibility to antibiotics was used in monitoring the emergence of gentamicin-resistant strains of aerobic and facultative gram-negative bacilli at Massachusetts General Hospital since the release of gentamicin for clinical use in 1971. During the period studied, there was a significant increase in the prevalence of gentamicin-resistant bacteria, particularly among Pseudomonas, Acinetobacter (Herellea), and Proteus and, more recently, among Enterobacter and Klebsiella. Most gentamicin-resistant strains of Pseudomonas aeruginosa and Acinetobacter calcoaceticus var. anitratum (Herellea varginicola) retained susceptibility to tobramycin. Of the other gentamicin-resistant organisms, most were also resistant to tobramycin. Twelve patients with infections caused by gentamicin-resistant organisms were treated with tobramycin. All 12 patients were seriously ill, and all but one had failed to respond to previous therapy with gentamicin. Nine patients responded favorably to tobramycin, and six were cured. P. aeruginosa and A. calcoaceticus var. anitratum were most frequently the infecting organisms in these patients. Patients received tobramycin for three to 42 days; no significant drug-related toxicity was noted. These results emphasize the increasing clinical importance of gentamicin-resistant bacteria and suggest that tobramycin may be effective for treatment of some, but not all, infections caused by gentamicin-resistant bacteria.

Acinetobacter↗
PubMed1997

Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various beta-lactam antibiotics.

OBJECTIVE: To determine the propensity of beta-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: Two open, randomized, double-blind, parallel-group studies were conducted in young, healthy, male volunteer subjects. Using a common protocol, 24-hour urine collections were analyzed for the renal tubular enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied included gentamicin plus placebo and gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobial regimens were administered for 7 days. Eight subjects completed each treatment group. RESULTS: There were no significant differences between treatment groups with regard to urine creatinine excretion or serum gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate treatment compared with that in the gentamicin plus placebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ceftazidime treatment (p < 0.05) compared with the other two treatments. CONCLUSIONS: Based on relative enzymuria, ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP and NAG reflect insults to the kidney, these studies suggest that ceftazidime may enhance aminoglycoside-induced renal injury. Piperacillin had no effect on enzymuria and would appear not to enhance or protect against aminoglycoside-induced renal injury.

Acetylglucosaminidase↗