In Vitro Bactericidal Effectiveness of Four Aminoglycoside Antibiotics

The antibacterial activity of four aminoglycoside antibiotics (gentamicin, Sch 13706, tobramycin, and sisomicin) was tested against eight gram-negative and three gram-positive species. A total of 323 strains were studied by the broth dilution technique. Tobramycin and sisomicin had greater bacteriostatic and bactericidal activity against Pseudomonas strains than did gentamicin and Sch 13706. Of the four antibiotics, sisomicin was most active against Klebsiella, Enterobacter, Escherichia coli, indole-negative and -positive Proteus, and Streptococcus pyogenes. Gentamicin was most effective against Serratia. A fourfold or greater difference existed frequently between the minimal inhibitory and bactericidal concentrations of all antibiotics against Enterobacter and Serratia. This difference was greatest with tobramycin. Staphylococcus aureus was highly susceptible, Providencia relatively resistant, and enterococcus uniformly resistant to the antibiotics studied. Agar diffusion susceptibility testing with gentamicin and tobramycin showed that organisms susceptible to less than 6.2 mug/ml usually yielded zones 17 to 26 mm in diameters. Zones of 15 to 16 mm represented intermediate susceptibility which varied with the organism and antibiotic. Several Serratia strains required 6.2 to 12.5 mug of gentamicin/ml or 25 to 50 mug of tobramycin/ml for bactericidal activity despite minimal inhibitory concentrations of 0.09 to 3.1 mug/ml and zone sizes greater than 13 and 17 mm, respectively. Studies with Enterobacter and tobramycin yielded similar results.     

The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment

We have measured the in-vitro activity of 27 antimicrobials against 211 clinical and ten reference strains of Pseudomonas pseudomallei. Imipenem was the most active antibiotic tested, followed by piperacillin, doxycycline, amoxycillin/clavulanic acid, cefixime, cefetamet, azlocillin and ceftazidime, all of which had MICs of less than or equal to 2 mg/l for the majority of strains. The measured MICs were dependent on the media and inocula used, to an extent which varied with the antibiotic class under test; MICs of ureidopenicillins were particularly inoculum-dependent. The beta-lactams and ciprofloxacin were bactericidal, whereas the agents conventionally used to treat melioidosis (doxycycline, chloramphenicol, sulphamethoxazole and trimethoprim) had bacteriostatic activity only. Strains highly resistant to chloramphenicol (MIC greater than or equal to 256 mg/l) emerged during treatment in 7.1% of patients. These strains were fully virulent, and frequently showed cross-resistance to tetracyclines, sulphamethoxazole, trimethoprim and ciprofloxacin, with paradoxical increased susceptibility to beta-lactams and aminoglycosides. Similar resistance patterns were seen in mutants generated in vitro and two reference strains. One strain with isolated ceftazidime resistance, reversible by clavulanic acid, emerged during treatment. Several of the new beta-lactam antibiotics are of potential value in the therapy of P. pseudomallei infections. Patients should be carefully monitored for the emergence of antibiotic-resistant strains during treatment of melioidosis.     

In vitro studies of investigational beta-lactams as possible therapy for Pseudomonas aeruginosa endocarditis.

The inadequacy of the present medical therapy of Pseudomonas aeruginosa endocarditis prompted an investigation of the in vitro activities of aztreonam, cefsulodin, and imipenem compared with that of ticarcillin against 37 strains of P. aeruginosa isolated from patients with endocarditis. Inhibitory and bactericidal activities were studied for each beta-lactam alone and in combination with tobramycin. All agents showed excellent inhibitory activity. Imipenem was the most inhibitory beta-lactam yet lacked inhibitory synergy against 95% of the strains and bactericidal synergy against 62%. Tolerance to imipenem was seen in six strains. Aztreonam alone was bactericidal against 46% of the strains (at 16 micrograms/ml) and showed bactericidal synergy in 70%. Cefsulodin alone was even less active but similar to aztreonam synergistically. Ticarcillin and tobramycin inhibited all strains as single agents and showed universal bactericidal synergy in combination. None of the new beta-lactams showed consistent superiority to the presently used agent, ticarcillin.     

Antibacterial activity of ticarcillin, tobramycin and gentamicin alone and in combination against Pseudomonas aeruginosa in vitro.

Using the biophotometer with ticarcillin no persistent bactericidal effect was found against Pseudomonas aeruginosa NCTC 10490. After addition of 1.2 microgram/ml gentamicin an increase of multiplication of bacteria was observed, but not after 1.2 microgram/ml tobramycin. With 6.2 microgram/ml tobramycin bactericidal effects lasted more than 24 h. In tube dilution test with Isotonic Sensi-test Broth out of 109 examined strains 51% were resistant to gentamicin, 16% to tobramycin and 4.5% to ticarcillin. If MIC values of gentamicin and tobramycin were calculated for magnesium-free media the resistance rate would be 10% for gentamicin and 3% for tobramycin. Combining subinhibitory doses of gentamicin or tobramycin with ticarcillin, most of the strains resistant to gentamicin and tobramycin became susceptible. The rate of inactivation of tobramycin by ticarcillin depends on the fluid into which they are placed. In combination therapy both antibiotics should be applied separately and immediately one after the other.     

In vitro efficacy of Bay k 4999, a new ureido-penicillin, in combination with aminoglycosides against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Proteus strains.

The in vitro effects of Bay k 4999 in combination with gentamicin, tobramycin, amikacin sisomicin and netilmicin in bacteriostatic (MIC) and bactericidal (MBC) concentrations were compared using the checkerboard dilution technique against 20 different strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and indole-positive-negative Proteus species. On average 63% of Bay k 4999-aminoglycoside (AG) combinations inhibited Pseudomonas, Proteus and Klebsiella strains additively and/or synergistically in bacteriostatic as well as in bactericidal concentrations as compared to only 14% additive or synergistic activity on E. coli. 35% of the combinations tested proved to be synergistic in K. pneumoniae, 20% in Proteus, 13% in Pseudomonas, but only 5% in E. coli. No significant differences between various Bay k 4999-AG combination effects could be demonstrated.     

The in-vitro activity of linezolid (U-100766) and tentative breakpoints

The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs (MIC90 within one dilution step) of linezolid and an increase in inoculum from 10(5) to 10(7) cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.     

Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem

We determined the in vitro activities of tigecycline and imipenem against 49 isolates of Acinetobacter baumannii, including those resistant to imipenem. The MIC at which 50% of the isolates were inhibited (MIC(50)) and the MIC(90) for tigecycline and imipenem were 2 and 2 mg/liter and 32 and 128 mg/liter, respectively, with 92 and 20%, respectively, of the strains being susceptible. Tigecycline did not show bactericidal activity in the time-kill studies (n = 9 strains). Imipenem showed bactericidal activity against seven out of nine strains. These in vitro results show that tigecycline has good in vitro bacteriostatic activity against A. baumannii, including strains resistant to imipenem.     

Effect of peritoneal dialysis fluid and pH on bactericidal activity of ciprofloxacin.

Ciprofloxacin is active in vitro against most bacteria that cause peritonitis associated with peritoneal dialysis. We compared the effects of pH (5.5 and 7.4) and medium (dialysis fluid) on the bactericidal activity of ciprofloxacin, tobramycin, vancomycin plus rifampin, and rifampin against Pseudomonas aeruginosa, Escherichia coli, and three strains of staphylococci. The bactericidal activity of ciprofloxacin was not significantly affected by pH or medium, in contrast to the activity of tobramycin, which was decreased by low pH.     

Emergence of 4'',4"-aminoglycoside nucleotidyltransferase in enterococci.

Enterococcus faecium BM4102 was resistant to macrolide-lincosamide-streptogramin B-type (MLS) antibiotics; tetracycline-minocycline; and high levels of kanamycin, neomycin, tobramycin, and dibekacin but not gentamicin. This aminoglycoside resistance phenotype is new in enterococci. The genes conferring resistance to aminoglycosides and MLS antibiotics in this strain were carried on a plasmid, pIP810, that was self-transferable to to other Enterococcus strains. Resistance to tobramycin and structurally related aminoglycosides, kanamycin, neomycin, and dibekacin, was due to synthesis of a 4',4"-aminoglycoside nucleotidyltransferase. Homology was detected by hybridization between pIP810 DNA and a probe specific for a gene encoding an enzyme with identical site specificity in staphylococci. The bacteriostatic activity of amikacin apparently was not affected by the presence of the enzyme, although it was modified in vitro. However, the bactericidal activity of amikacin and the synergism of this aminoglycoside with penicillin were abolished.     

Activities of oral and parenteral agents against penicillin-susceptible and -resistant pneumococci.

This study examined bacteriostatic and bactericidal activities of oral and parenteral antibiotics for penicillin-susceptible and intermediately and fully penicillin-resistant pneumococci. beta-Lactamase inhibitors did not affect beta-lactam results. The activities of ampicillin, amoxicillin +/- clavulanate, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime, and cefaclor against two penicillin-susceptible, two intermediately penicillin-resistant, and two fully penicillin-resistant pneumococcal strains were tested. For all three groups, bacteriostatic values of amoxicillin and WY-49605 were lower than were those of other beta-lactams tested. Of the cephalosporins, cefdinir, cefuroxime, and cefpodoxime yielded the lowest bacteriostatic values. All beta-lactams were bactericidal (reduced original counts by > or = 3 log10 CFU/ml) at 1 dilution above bacteriostatic values, except for cefpodoxime (bactericidal at 2 dilutions above bacteriostatic values for one susceptible strain and one intermediately resistant strain), cefuroxime (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain), and ampicillin (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain). The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftriaxone, ceftazidime, and ciprofloxacin against four penicillin-susceptible, two intermediately penicillin-resistant, and four fully penicillin-resistant pneumococcal strains were evaluated. Bacteriostatic values of piperacillin, ampicillin, and ceftriaxone for all groups were lower than were those of ticarcillin and ceftazidime. Bacteriostatic values of ciprofloxacin were unaffected by penicillin susceptibility. All beta-lactams were bactericidal at 1 dilution above the bacteriostatic value, except for piperacillin (bactericidal at 2 dilutions above the bacteriostatic value for one intermediately resistant strain), ticarcillin (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain and one resistant strain), ampicillin (bactericidal at 2 dilutions above the bacteriostatic value for two resistant strains), ceftriaxone (bactericidal at 2 dilutions above the bacteriostatic value for one resistant strain), and ceftazidime (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain).     

Antipneumococcal activity of AZD2563, a new oxazolidinone,compared with nine other agents

The in vitro activity of AZD2563, a new oxazolidinone, was compared with that of linezolid, vancomycin, quinupristin/dalfopristin, amoxicillin, levofloxacin, penicillin, erythromycin, azithromycin and clindamycin against a range of pneumococci by microdilution and time-kill studies. Against 300 pneumococci (99 penicillin susceptible, 86 penicillin intermediate, 115 penicillin resistant, 185 erythromycin resistant, 35 quinolone resistant), both oxazolidinones remained active against isolates less susceptible to other agents, with MICs ranging between 0.125 and 2 mg/L; AZD2563 MICs were generally one dilution lower than those of linezolid. Both quinupristin/dalfopristin and vancomycin were active against all groups (MIC ranges 0.125-2 and 0.125-0.25 mg/L, respectively). Apart from 35 isolates with levofloxacin MICs > or= 8 mg/L, levofloxacin MICs were < or =0.25-4 mg/L. MICs of amoxicillin and erythromycin rose with penicillin G MICs; most macrolide-resistant isolates were either penicillin-intermediate or -resistant. Against 16 organisms with differing beta-lactam, macrolide and quinolone MICs, time-kill studies showed that AZD2563 was bactericidal (99.9% killing) at 4 x MIC against nine strains at 24 h, with 90% killing of all 16 strains at 2 x MIC after 12 h. Similar results were obtained with linezolid. Both oxazolidinones were bacteriostatic at the MIC against all 16 strains. Amoxicillin, levofloxacin and vancomycin, at 2 x MIC, were bactericidal against 15 of the 16 strains after 24 h. Quinupristin/dalfopristin yielded the most rapid killing, with bactericidal activity against 13 of 16 strains at the MIC after 3 h and against 15 strains at 2 x MIC after 24 h. Erythromycin was bactericidal against all 10 strains with MICs < or= 8 mg/L at 4 x MIC after 24 h.     

Therapy of staphylococcal infections with cefamandole or vancomycin alone or with a combination of cefamandole and tobramycin.

Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.     

In vitro activity of LY146032 against gram-positive bacteria

The activity of LY146032 (LY) was evaluated against 269 clinical isolates: 150 Staphylococcus spp. (Staph), 45 enterococci, 51 Clostridium spp., and 23 peptostreptococci. LY was compared to penicillin, metronidazole, imipenem, clindamycin, oxacillin, ciprofloxacin, vancomycin, and ampicillin. LY and oxacillin were tested against Staph by microdilution in cation-supplemented Mueller-Hinton broth (CSMHB), and in unsupplemented Mueller-Hinton broth (MHB). For LY, the MIC 90s in CSMHB were 16-32 dilutions lower. Among the Staph, the MIC 90s for LY, vancomycin, and ciprofloxacin were 4 micrograms/ml, 4 micrograms/ml, and 2 micrograms/ml respectively. The MIC 90s for enterococci by agar dilution were as follows: LY 8 micrograms/ml; ampicillin 4 micrograms/ml; imipenem 4 micrograms/ml; vancomycin 4 micrograms/ml; and ciprofloxacin 2 micrograms/ml. Clindamycin and penicillin were the most effective drugs against peptostreptococci and Clostridia spp., but LY was the most active drug against Clostridium difficile. The bactericidal activity of LY was determined by 24-hr time-kill curves in MHB. These showed a bactericidal effect against enterococci, and a bacteriostatic effect against three of four strains of Staph. Synergy was demonstrated against enterococci and Staph when LY was tested with aztreonam, ceftriaxone, or tobramycin. LY is a promising new agent against gram-positive bacteria, including methicillin resistant strains of staphylococci and enterococci.     

Comparative activities of ampicillin, epicillin and amoxycillin in vitro and in vivo.

The antibacterial activities of three aminopenicillins ampicillin, epicillin and amoxycillin were compared in vitro and in vivo. The minimum inhibitory concentrations (MIC) of the three penicillins were very similar and the compounds were active against non-beta-lactamase-producing strains of Escherichia coli, Salmonella and Shigella species, Proteus mirabilis, Haemophilus influenzae and Neisseria gonorrhoeae. Streptococci including Streptococcus faecalis, and non-beta-lactamase-producing staphylococci were also sensitive to the compounds but Pseudomonas aeruginosa, Klebsiella aerogenes, Enterobacter and indole-positive Proteus species were resistant. At concentrations close to MIC value epicillin and ampicillin showed similar bactericidal activity against E. coli and against S. typhi and both compounds caused a slower rate of kill than was seen with amoxycillin. Microscopical observation of the cells exposed to ampicillin and epicillin for 1 h showed the presence of filamentous forms which lysed slowly, whereas cells exposed to amoxycillin for the same period rapidly. Epicillin was similar to or slightly less active than ampicillin against experimental mouse infections, and against the majority of infections both compounds were significantly less effective than amoxycillin by the oral and subcutaneous routes of administration.     

Laboratory studies on coagulase-negative staphylococci from CAPD-associated peritonitis

This study compared the static and kinetic activities, in both broth and used-dialysate, of selected antibiotics against 23 strains of coagulase-negative staphylococci causing peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). Vancomycin was shown to be effective against all isolates with similar rates of kill to flucloxacillin and cefuroxime, although a few strains were found to be resistant to cefuroxime. Gentamicin was rapidly bactericidal for sensitive strains which accounted for 60% of the strains tested. Fusidic acid was associated with significant resistance and lack of bactericidal activity in the kinetic studies. Emergence of resistance occurred with rifampicin. The combinations clavulanic acid/amoxycillin and sulbactam/ampicillin generally showed good static activity. In addition a broad range of biotypes and phage types were demonstrated among these organisms with biotype SII (Staphylococcus epidermidis) predominating. There was no correlation between biotype and antibiogram.     

Resistance in oral streptococci after repeated two-dose amoxycillin prophylaxis

Twelve normal volunteers received two doses of 3 g amoxycillin at weekly intervals on up to five occasions. Amoxycillin-resistant oral streptococci were not isolated from any subject beforehand, but they had appeared in all eleven subjects (who could be included in the analysis) by the end of the investigation, and in one subject after one administration of double dose amoxycillin. Resistant streptococci were undetectable in all volunteers 13 weeks after their last dose of amoxycillin. All resistant streptococci identified were Streptococcus sanguis (non-dextran-producing), many were highly resistant to amoxycillin and some were also moderately resistant to erythromycin. The minimum bactericidal concentrations for the most resistant streptococcal strains isolated were less than the peak serum amoxycillin concentrations expected following a 3 g oral dose of amoxycillin. In the majority of volunteers the counts of oral resistant streptococci had greatly declined by about 6 weeks following the last administration of a double dose of amoxycillin. If further dental treatment liable to cause bacteraemia is required within six weeks of double dose amoxycillin prophylaxis an alternative regimen should be sought.     

In Vitro Evaluation of Tobramycin, a New Aminoglycoside Antibiotic

One hundred fifty-two strains of Escherichia coli, Klebsiella-Enterobacter, Pseudomonas aeruginosa, Proteus species, and Staphylococcus aureus were inhibited by 3.1 mug of tobramycin/ml in a broth-dilution method and showed zones of inhibition of 16 mm or more around a 10-mug tobramycin disc in the Kirby-Bauer method. Tobramycin was most active against S. aureus, 100% of strains being inhibited by 0.1 mug/ml. All strains of E. coli, K. pneumoniae, P. aeruginosa, and indole-positive Proteus species, and 80% of Enterobacter species were inhibited by 0.8 mug of tobramycin/ml, whereas only 48% of P. mirabilis strains were inhibited by this concentration. Tobramycin was approximately twice as active as gentamicin against S. aureus, four times as active against P. aeruginosa, slightly more active against E. coli and Enterobacter species, equally active against P. mirabilis, and slightly less active against K. pneumoniae. The minimal bactericidal concentrations of tobramycin and gentamicin were the same as or twice the minimal inhibitory concentrations for all strains except those of P. aeruginosa, against which greater concentrations of both gentamicin and tobramycin were required for bactericidal activity. Tobramycin sterilized cultures of S. aureus, E. coli, and P. aeruginosa, but the rate of bactericidal action was faster with a combination of tobramycin and carbenicillin than with either antibiotic alone in the same concentrations. Tobramycin retained potency in the presence of 200 to 600 mug of carbenicillin/ml for at least 6 hr of incubation at 37 C, but lost potency in the presence of 600 mug of carbenicillin/ml by 24 hr of incubation and in the presence of 800 mug/ml by 2 hr of incubation.     

Activity of pirlimycin (U57930E) against strains of the Bacteroides fragilis group.

The activities of pirlimycin (U57930E), lincomycin, clindamycin, erythromycin, josamycin, oleandomycin, and spiramycin were compared against strains of the Bacteroides fragilis group. Pirlimycin was the most active; the 90% minimal inhibitory concentration was 1 microgram/ml, and the activity range was 0.125 to 4 micrograms/ml. This drug was fourfold more active than any of the other drugs, including clindamycin. The minimal bactericidal concentration (range, 0.5 to 16 micrograms/ml) shows that pirlimycin behaves as a bacteriostatic antibiotic.     

In Vitro Studies with Sch 21420 and Sch 22591: Activity in Comparison with Six Other Aminoglycosides and Synergy with Penicillin Against Enterococci

In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against Staphylococcus aureus, Enterobacteriaceae, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against Pseudomonas aeruginosa. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against S. aureus and most genera of Enterobacteriaceae. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against Proteus rettgeri and Providencia stuartii, but (ii) less active than the other five aminoglycosides against Neisseria gonorrhoeae, enterococci, most nonfermenting gram-negative bacilli, Proteus mirabilis, and Proteus morganii. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 μg of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 μg/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.     

Chemotherapeutic Evaluation of 5-Episisomicin (Sch 22591), a New Semisynthetic Aminoglycoside

5-episisomicin (Sch 22591) is a novel semisynthetic aminoglycoside with a spectrum and potency similar to gentamicin in its activity against susceptible bacterial strains, but with increased potency against Pseudomonas, Providencia, and Proteus rettgeri. It is also more active than tobramycin and amikacin against these last-mentioned species.Against resistant strains, Sch 22591 is significantly more active than gentamicin or tobramycin. Against resistant gram-negative bacteria other than Pseudomonas, Sch 22591 has activity similar to that of amikacin, but Sch 22591 is more potent. Against Pseudomonas strains, it is active against most gentamicin- and tobramycin-resistant strains and is more active than the other three antibiotics. Some Pseudomonas strains are resistant to Sch 22591, but susceptible to amikacin. Against a selection of aminoglycoside-resistant staphylococci, Sch 22591 has very good activity against strains resistant to tobramycin, amikacin, and gentamicin. The superior in vitro potency of Sch 22591 against Pseudomonas has been confirmed in vivo in experimental infections in mice. Absorption in dogs is similar to that of other aminoglycoside antibiotics. The acute toxicity of Sch 22591 in mice is greater than that of gentamicin; its vestibular toxicity potential and nephrotoxicity potential in cats and rats appear to be similar to those of gentamicin.