Clinical Usefulness of Arbekacin / 감염과화학요법

Arbekacin is a broad-spectrum aminoglycoside used to treat methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin has antibacterial activities against high-level gentamicin-resistant Enterococci, multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii et al. Here, we reviewed in vitro data on arbekacin in Staphylococci and Gram-negative microorganisms. We also reviewed clinical studies for clinical efficacy and microbiologic efficacy data in patients with identified MRSA and suspected MRSA infections. The overall clinical efficacy ranged from 66.7% to 89.7%. The microbiologic efficacy rate ranged from 46.2% to 83%. In comparative studies between arbekacin and glycopeptides, arbekacin was similar to other glycopeptides with respect to clinical and microbiological efficacy rates. Combination trials with other antibiotics suggest that arbekacin will be a promising strategy to control Enterococcus spp. multi-drug resistant P. aeruginosa. The major adverse reaction was nephrotoxicity/hepatotoxicity, but patients recovered from most adverse reactions without any severe complications. Based on these results, arbekacin could be a good alternative to vancomycin/teicoplanin in MRSA treatment. Finally, therapeutic drug monitoring is recommended to maximize clinical efficacy and decrease nephrotoxicity.

Comparison of Arbekacin and Vancomycin in Treatment of Chronic Suppurative Otitis Media by Methicillin Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ear infections. We attempted to evaluate the clinical usefulness of arbekacin in treating chronic suppurative otitis media (CSOM) by comparing its clinical efficacy and toxicity with those of vancomycin. Efficacy was classified according to bacterial elimination or bacteriologic failure and improved or failed clinical efficacy response. Ninety-five subjects were diagnosed with CSOM caused by MRSA. Twenty of these subjects were treated with arbekacin, and 36 with vancomycin. The bacteriological efficacy (bacterial elimination, arbekacin vs. vancomycin: 85.0% vs. 97.2%) and improved clinical efficacy (arbekacin vs. vancomycin; 90.0% vs. 97.2%) were not different between the two groups. However, the rate of complications was higher in the vancomycin group (33.3%) than in the arbekacin group (5.0%) (P=0.020). In addition, a total of 12 adverse reactions were observed in the vancomycin group; two for hepatotoxicity, one for nephrotoxicity, eight for leukopenia, two for skin rash, and one for drug fever. It is suggested that arbekacin be a good alternative drug to vancomycin in treatment of CSOM caused by MRSA.

The Efficacy and Safety of Arbekacin and Vancomycin for the Treatment in Skin and Soft Tissue MRSA Infection: Preliminary Study / 감염과화학요법

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become a one of the most important causes of nosocomial infections, and use of vancomycin for the treatment of MRSA infection has increased. Unfortunately, vancomycin-resistant enterococcus have been reported, as well as vancomycin-resistant S. aureus. Arbekacin is an antibacterial agent and belongs to the aminoglycoside family of antibiotics. It was introduced to treat MRSA infection. We studied the clinical and bacteriological efficacy and safety of arbekacin compared to vancomycin in the treatment of infections caused by MRSA. MATERIALS AND METHODS: This was a retrospective case-control study of patients who were admitted to tertiary Hospital from January 1st, 2009 to December 31st, 2010, and received the antibiotics arbekacin or vancomycin. All the skin and soft tissue MRSA infected patients who received arbekacin or vancomycin were enrolled during the study period. The bacteriological efficacy response (BER) was classified with improved and failure. The improved BER was defined as no growth of MRSA, where failure was defined as growth of MRSA, culture at the end of therapy or during treatment. Clinical efficacy response (CER) was classified as improved and failure. Improved CER was defined as resolution or reduction of the majority of signs and symptoms related to the original infection. Failure was defined as no resolution and no reduction of majority of the signs and symptoms, or worsening of one or more signs and symptoms, or new symptoms or signs associated with the original infection or a new infection. RESULTS: Totally, 122 patients (63/99 in arbekacin, 59/168 in vancomycin group) with skin and soft tissue infection who recieved arbekacin or vancomcyin at least 4 days were enrolled and analysed. The bacteriological efficacy response [improved, arbekacin vs vancomycin; 73.0% (46/63), 95% confidence interval (CI) 60.3 to 83.4% vs 83.1% (49/59), 95% CI 71.0 to 91.6%] and clinical efficacy response [improved, arbekacin vs vancomycin; 67.2% (41/61), 95% CI 52.0 to 76.7% vs 78.0% (46/59), 95% CI 65.3 to 87.7%] were similar between the two groups (P=0.264, 0.265). The complication rate was significantly higher in the vancomycin group [29/59(49.2%), 95% CI 35.9 to 62.5%] than arbekacin [10/63(15.9%), 95% CI 8.4 to 29.0%] (P<0.001). CONCLUSIONS: Arbekacin could be considered as an alternative antibiotics for vancomycin in skin and soft tissue infection with MRSA. However, further prospective randomized trials are needed to confirm this finding.

Efficacy of the Arbekacin and Teicoplanin Combination on Glycopeptide Intermediate Staphylococcus aureus in a Rabbit Model of Endocarditis / 감염과화학요법

BACKGROUND: There have been no reports to evaluate the usefulness of combination therapy with glycopeptide and arbekacin in endocarditis by in vivo model. MATERIALS AND METHODS: We investigated the efficacy of the arbekacin and teicoplanin combination on glycopeptide intermediate Staphylococcus aureus (GISA) in rabbit model of endocardits. GISA Mu50 strain was used for the experiment. The rabbit model of aortic valve endocarditis as described previously was used. Treatment was started 20h later inoculation with teicoplanin alone (at 20 mg/kg of body weight intramuscularly every 12 hours for 4 days after loading dose of 40 mg/kg of body weight intramuscularly), arbekacin alone (5 mg/kg of body weight intramuscularly every 12h for 4 days), or teicoplanin plus arbekacin. The results of therapy for experimental endocarditis due to Mu50 showed that teicoplanin and arbekacin combination was more effective than the administration of both drugs alone in reducing the log10CFU/g of aortic vegetation (P<0.05). CONCLUSION: The combination of teicoplanin and arbekacin was more effective against GISA (Mu50) than both drugs alone in vivo endocarditis model.

Efficacy of the Arbekacin and Teicoplanin Combination on Glycopeptide Intermediate Staphylococcus aureus in a Rabbit Model of Endocarditis / 감염과화학요법

BACKGROUND: There have been no reports to evaluate the usefulness of combination therapy with glycopeptide and arbekacin in endocarditis by in vivo model. MATERIALS AND METHODS: We investigated the efficacy of the arbekacin and teicoplanin combination on glycopeptide intermediate Staphylococcus aureus (GISA) in rabbit model of endocardits. GISA Mu50 strain was used for the experiment. The rabbit model of aortic valve endocarditis as described previously was used. Treatment was started 20h later inoculation with teicoplanin alone (at 20 mg/kg of body weight intramuscularly every 12 hours for 4 days after loading dose of 40 mg/kg of body weight intramuscularly), arbekacin alone (5 mg/kg of body weight intramuscularly every 12h for 4 days), or teicoplanin plus arbekacin. The results of therapy for experimental endocarditis due to Mu50 showed that teicoplanin and arbekacin combination was more effective than the administration of both drugs alone in reducing the log10CFU/g of aortic vegetation (P<0.05). CONCLUSION: The combination of teicoplanin and arbekacin was more effective against GISA (Mu50) than both drugs alone in vivo endocarditis model.

In Vitro Activity of Arbekacin Against Clinical Isolates of Staphylococcus species and Gram-negative Bacilli / 대한진단검사의학회지

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram-negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed infections, and are often resistant to multiple drugs. Arbekacin is an aminoglycoside used for the treatment of MRSA infections, but is also active against some gram-negative bacilli. The aim of this study was to determine in vitro activity of arbekacin against recent clinical isolates of staphylococci and gram-negative bacilli. Materials and METHODS: The strains were isolated from clinical specimens of patients at Severance Hospital in 2003. Antimicrobial susceptibility was tested by the Clinical and Laboratory Standards Institute agar dilution method. The following arbekacin breakpoints were used: susceptible, or =16 microgram/mL . RESULTS: All isolates of staphylococci tested were inhibited by 32-fold and >32-128-fold lower than those of amikacin and gentamicin, respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus, methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin-susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter freundii, 1 microgram/mL and 16 microgram/mL, were 2-4-fold and 8-16-fold lower than those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin for other species of gram-negative bacilli, 64->128 microgram/mL, were similar to those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful alternative to glycopeptides for the treatment of monomicrobial methicillin-resistant staphylococcal infections, as well as mixed infections with gram-negative bacilli, as most isolates of E. coli, C. freundii and some other gram-negative bacilli were also susceptible to arbekacin.

In Vitro Activity of Arbekacin Against Clinical Isolates of Staphylococcus species and Gram-negative Bacilli / 대한진단검사의학회지

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram-negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed infections, and are often resistant to multiple drugs. Arbekacin is an aminoglycoside used for the treatment of MRSA infections, but is also active against some gram-negative bacilli. The aim of this study was to determine in vitro activity of arbekacin against recent clinical isolates of staphylococci and gram-negative bacilli. Materials and METHODS: The strains were isolated from clinical specimens of patients at Severance Hospital in 2003. Antimicrobial susceptibility was tested by the Clinical and Laboratory Standards Institute agar dilution method. The following arbekacin breakpoints were used: susceptible, or =16 microgram/mL . RESULTS: All isolates of staphylococci tested were inhibited by 32-fold and >32-128-fold lower than those of amikacin and gentamicin, respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus, methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin-susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter freundii, 1 microgram/mL and 16 microgram/mL, were 2-4-fold and 8-16-fold lower than those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin for other species of gram-negative bacilli, 64->128 microgram/mL, were similar to those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful alternative to glycopeptides for the treatment of monomicrobial methicillin-resistant staphylococcal infections, as well as mixed infections with gram-negative bacilli, as most isolates of E. coli, C. freundii and some other gram-negative bacilli were also susceptible to arbekacin.

Once-daily Dosing of Arbekacin Can Suppress the Formation of Small Colony Variants of Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Infection Model / 감염과화학요법

BACKGROUND: Small colony variants (SCVs) of Staphylococcus aureus have emerged to be commonly associated with persistent and relapsing infections. Arbekacin (ABK) is one of a few alternatives to vancomycin in intractable case of methicillin resistant S. aureus (MRSA) infection. However, it has not yet been defined whethter ABK tends to be efficacious to the MRSA SCVs. In this study, we employed an in vitro pharmacodynamic infection model (IVPDIM) to define efficacies of ABK against MRSA SCVs. MATERIALS AND METHODS: Using four strains of clinically isolated MRSA (MRSA122, MRSA160, MRSA18, MRSA123), we adopted IVPDIM comprised of two-compartment in which effective surface-to-volume ratio of 5.34 cm(-1). Human pharmacokinetic regimen simulations of ABK were as follows: 100 mg every 12 h (q12h), 200 mg q24h, 200 mg q12h, and 400 mg q24h. Samples were taken from each model at 0, 1, 2, 4, 6, 12, 24, and 30 h, and the bacterial colony counts were determined. The experiments were repeated twice with ABK-administered groups and control group. RESULTS: MICs of ABK for MRSA122, MRSA160, MRSA18, and MRSA123 were 2, 2, 2, and 1 microgram/mL, respectively. In case of MRSA122, MRSA160, MRSA18, C(max)/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, C(max)/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed C(max)/MIC >9. Four regimens for 4 strains showed statistically different colony counts at 30 h (P=0.000). The more dosage or less frequent dosing interval, the more colonies tended to reduce in all strains. In 100 mg q12h groups, SCVs were observed in all strains within 24 h. With increment of dosage or changing dosing interval from q12h to 24h, SCVs were reduced (P=0.000). Regimen of 400 mg q24h did not let SCVs appear in all strains of MIC 2 microgram/mL during the experiments. CONCLUSION: SCVs were observed when MIC of ABK against MRSA were 1-2 microgram/mL, especially in most cases of C(max)/MIC <9. Those findings were also associated with re-growth of colony during the experiments. Once-daily dosing of ABK could reduce or eliminate the appearance of SCV.

Once-daily Dosing of Arbekacin Can Suppress the Formation of Small Colony Variants of Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Infection Model / 감염과화학요법

BACKGROUND: Small colony variants (SCVs) of Staphylococcus aureus have emerged to be commonly associated with persistent and relapsing infections. Arbekacin (ABK) is one of a few alternatives to vancomycin in intractable case of methicillin resistant S. aureus (MRSA) infection. However, it has not yet been defined whethter ABK tends to be efficacious to the MRSA SCVs. In this study, we employed an in vitro pharmacodynamic infection model (IVPDIM) to define efficacies of ABK against MRSA SCVs. MATERIALS AND METHODS: Using four strains of clinically isolated MRSA (MRSA122, MRSA160, MRSA18, MRSA123), we adopted IVPDIM comprised of two-compartment in which effective surface-to-volume ratio of 5.34 cm(-1). Human pharmacokinetic regimen simulations of ABK were as follows: 100 mg every 12 h (q12h), 200 mg q24h, 200 mg q12h, and 400 mg q24h. Samples were taken from each model at 0, 1, 2, 4, 6, 12, 24, and 30 h, and the bacterial colony counts were determined. The experiments were repeated twice with ABK-administered groups and control group. RESULTS: MICs of ABK for MRSA122, MRSA160, MRSA18, and MRSA123 were 2, 2, 2, and 1 microgram/mL, respectively. In case of MRSA122, MRSA160, MRSA18, C(max)/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, C(max)/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed C(max)/MIC >9. Four regimens for 4 strains showed statistically different colony counts at 30 h (P=0.000). The more dosage or less frequent dosing interval, the more colonies tended to reduce in all strains. In 100 mg q12h groups, SCVs were observed in all strains within 24 h. With increment of dosage or changing dosing interval from q12h to 24h, SCVs were reduced (P=0.000). Regimen of 400 mg q24h did not let SCVs appear in all strains of MIC 2 microgram/mL during the experiments. CONCLUSION: SCVs were observed when MIC of ABK against MRSA were 1-2 microgram/mL, especially in most cases of C(max)/MIC <9. Those findings were also associated with re-growth of colony during the experiments. Once-daily dosing of ABK could reduce or eliminate the appearance of SCV.

Antimicrobial Activities of Arbekacin against Recent Isolates of Staphylococcus aureus in Korean Hospitals / 대한임상미생물학회지

BACKGROUND: As clinical isolates of Staphylococcus aureus with reduced inhibition zone of arbekacin in disk diffusion susceptibility tests are observed frequently, we examined their susceptibility to the antibiotic by comparing the results of the agar dilution testing with those of disk diffusion testing. METHODS: During the period of May through July, 2004, 88 isolates of methicillin-resistant and 11 methicillin-susceptible S. aureus were collected from clinical specimens in Pusan National University Hospital and Kosin University Gospel Hospital. Minimal inhibitory concentrations (MICs) of arbekacin were determined by the agar dilution method, and inhibition zones by the disk diffusion method. RESULTS: All of the 99 isolates were tested susceptible to arbekacin by the agar dilution method (MIC < or = 8 mg/L). By the disk diffusion method, however, 5 isolates (5.1%) were intermediate (minor error) and 2 isolates (2.0%) resistant (major error). CONCLUSION: All isolates were susceptible to arbekacin, but the disk diffusion method showed 7 per cent of minor or major errors.

Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

Efficacy of Vancomycin, Arbekacin, and Gentamicin Alone or in Combination Against Methicillin-Resistant Staphylococcus aureus in In Vitro Infective Endocarditis Model / 감염과화학요법

BACKGROUND: Glycopeptide has been used for the one-and-only treatment of choice in methicillin resistant Staphylococcus aureus (MRSA) infection, but its exclusive use for the MRSA infection has led to the increased risk of glycopeptide-resistance. To find an alternative (s), we employed an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VCM), arbekacin (ABK), and gentamicin (GM) alone or in combination. METHODS: Using two strains of clinically isolated MRSA, one GM susceptible (GS171) and the other GM resistant (GR153), fibrin clots were prepared and suspended in IVIEM. Antibiotics were added as a bolus to simulate human pharmacokinetics of regimens, including q 6 h, q 12 h, q 24 h, or continuous infusion with VCM, q 12 h or q 24 h with ABK, and q 8 h or q 24 h with GM. In cases of combination, regimens were VCM q 12 h plus ABK q 24 h, and VCM q 12 h plus GM q 24 h. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities (in CFU/g) were determined. RESULTS: At 8 hour, the colony counts of GS171 were lower than those of GR153 (P=0.02), and the lowest with the ABK q12h against GS171 (P=0.01). At 72 hour, monotherapy with ABK or VCM produced same degree of bacterial reductions in IVIEM, regardless of dosing frequency or GM-resistance. In the case of GM-resistance, combination of VCM and ABK did show additive effect until 24 hours, although VCM and GM showed no indifference during all the experiments. Development of resistance during experiment was not observed with any regimens. CONCLUSIONS: Our data suggest that ABK monotherapy could be used as an alternative to VCM even in the treatment of GM-resistant staphylococcal endocarditis. Further studies with clinical trials are warranted to evaluate the additive effect of VCM and ABK.

Efficacy of Vancomycin, Arbekacin, and Gentamicin Alone or in Combination Against Methicillin-Resistant Staphylococcus aureus in In Vitro Infective Endocarditis Model / 감염과화학요법

BACKGROUND: Glycopeptide has been used for the one-and-only treatment of choice in methicillin resistant Staphylococcus aureus (MRSA) infection, but its exclusive use for the MRSA infection has led to the increased risk of glycopeptide-resistance. To find an alternative (s), we employed an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VCM), arbekacin (ABK), and gentamicin (GM) alone or in combination. METHODS: Using two strains of clinically isolated MRSA, one GM susceptible (GS171) and the other GM resistant (GR153), fibrin clots were prepared and suspended in IVIEM. Antibiotics were added as a bolus to simulate human pharmacokinetics of regimens, including q 6 h, q 12 h, q 24 h, or continuous infusion with VCM, q 12 h or q 24 h with ABK, and q 8 h or q 24 h with GM. In cases of combination, regimens were VCM q 12 h plus ABK q 24 h, and VCM q 12 h plus GM q 24 h. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities (in CFU/g) were determined. RESULTS: At 8 hour, the colony counts of GS171 were lower than those of GR153 (P=0.02), and the lowest with the ABK q12h against GS171 (P=0.01). At 72 hour, monotherapy with ABK or VCM produced same degree of bacterial reductions in IVIEM, regardless of dosing frequency or GM-resistance. In the case of GM-resistance, combination of VCM and ABK did show additive effect until 24 hours, although VCM and GM showed no indifference during all the experiments. Development of resistance during experiment was not observed with any regimens. CONCLUSIONS: Our data suggest that ABK monotherapy could be used as an alternative to VCM even in the treatment of GM-resistant staphylococcal endocarditis. Further studies with clinical trials are warranted to evaluate the additive effect of VCM and ABK.

Clinical Efficacy and Safety with Arbekacin for Methicillin-Resistant Staphylococcus aureus (MRSA) Infections / 대한내과학회지

BACKGROUND: Arbekacin was introduced to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. It is an aminoglycoside with proven in vitro activity against MRSA strains. Pharmacokinetic advantages such as concentration-dependant bactericidal activity, prolonged post-antibiotic effect are its feature of aminoglycoside like others. But there are only few clinical data of this new kind of antibiotics outside of Japan, the first country approved its use against MRSA infections. We studied the clinical and bacteriological efficacy and safety of arbekacin in the treatment of infections caused by MRSA. METHODS: During the period between December 2001 and October 2002, we prospectively enrolled 21 patients with culture proven MRSA infection and evaluated the clinical and bacteriological efficacy and adverse events of arbekacin. Patients were treated with arbekacin sulphate 100 mg intravenously twice daily for 14 days. RESULTS: Patients were included if they had signs and symptoms of active MRSA infection including bacteremia, soft tissue infection, urinary tract infection, pneumonia etc. A total of 21 patients with MRSA infection were enrolled. Four patients experienced adverse events; 3 nephrotoxicities, 1 hepatotoxicity. One of them with elevated creatinine was unable to continue the study. Efficacy were evaluated on 19 patients with duration of arbekacin longer than 9 days. A favorable bacteriological response (eradicated or presumed eradicated) occurred in 13 (68.5%) patients. CONCLUSION: Although this clinical study was limited in number and in proper randomization, arbekacin alone was less effective than combination therapy with glycopeptides for the treatment of MRSA infection. However, our limited data suggested the efficacy of arbekacin alone for the treatment which needs shorter duration. The combination treatment of arbekacin and glycopeptide appeared to be less nephrotoxic than other aminoglycosides. The combination therapy of arbekacin and glycopeptide appeared to be less nephrotoxic than other aminoglycoside.

Frequency of Resistance to Aminog lycoside Antibiotics in Staphy lococcus aureus Isolated from Tertiary Hospitals / 감염

BACKGROUND: Staphylococcus aureus is one of the most important pathogens, causing severe morbidity and fatal infections. To date rapid evolution of antibiotic resistance in S. aureus, including recent emergence of vancomycin-resistant S. aureus (VRSA), has been a serious concern and an obstacle to the effective treatment. The purpose of this study is to update the resistance patterns against aminoglycoside antibiotics which play an important role in the therapy of serious staphylococcal infections. METHODS: Clinical isolates were collected from 8 university-affiliated hospitals during the period of June 1999 to January 2001. Susceptibility tests against 9 antibiotics were performed by disk diffusion method. Minimum inhibitory concentrations (MICs) of arbekacin against non-susceptible strains were determined by microbroth dilution method RESULTS: Among total 682 isolates exclusive of consecutive ones from the same patients, 199 (29%) were from pus, 152 (22%) from respiratory specimens, 137 (20%) from blood, 38 (6%) from urine. Of 682 isolates, 588 (87%) isolates were resistant to at least one of the aminoglycosides tested. Overall prevalence of MRSA was 64% (439/682), and resistance rates of MRSA were summarized as follows; kanamycin (KM) 98%, tobramycin (TOB) 98%, gentamicin (GM) 95%, amikacin (AMK) 90%, neomycin (NEO) 63%, streptomycin (SM) 31%, netilmicin (NET) 18%, arbekacin (ABK) 13%. MRSA isolates were resistant to multiple aminoglycosides, and 88% of them were resistant to all four aminoglycosides of KM, TOB, GM, and AMK. MICs of ABK against 58 non-susceptible strains ranged from 2 to 128 microgram/mL. CONCLUSION: More than 90% of MRSA isolates were resistant against kanamycin, tobramycin, gentamicin, and amikacin. Moreover, most of MRSA isolates were multi-drug resistant to all these four aminoglycosides. Resistance rates against arbekacin and netilmicin were less than 20%. Arbekacin was the most susceptible antibiotic of the aminoglycosides tested.

Antimicrobial Activities of Arbekacin against Clinical Isolates of Staphylococcus aureus and Coagulase-Negative Staphylococcus Species / 감염

BACKGROUND: Most strains of methicillin-resistant Staphylococcus aureus (MRSA) now exhibit high-level resistance to various antibiotics, such as beta-lactam antibiotics, aminoglycosides, macrolides, tetracyclines and quinolones. Recent reports describing the therapeutic failure of vancomycin for MRSA infections have arisen considerable concerns regarding the emergence of MRSA strains, which will require new therapeutic agents. Arbekacin, an aminoglycoside antibiotic, has antibacterial activity against both gram-positive and gram-negative bacteria and is stable in the presence of aminoglycoside inactivating enzymes produced by S. aureus. In this study, we compared the antibacterial activity of arbekacin with those of vancomycin, gentamicin, and amikacin against Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci (CNS). METHODS: For a collection of 549 S. aureus and 251 CNS isolates from three Catholic University Hospitals in Korea, minimum inhibitory concentrations (MICs) of arbekacin, vancomycin, amikacin and gentamicin were determined by agar dilution method using Mueller-Hinton agar according to NCCLS (National Committee for Clinical Laboratory Standards, USA) criteria. RESULTS: Among 549 S. aureus isolates, 278 isolates were MRSA and 271 isolates were methicillin- sensitive S. aureus (MSSA). MIC50 & MIC90 of arbekacin against 549 S. aureus were 0.5 & 1 microgram/mL, and MIC50 & MIC90 of vancomycin were 1 & 1 microgram/ mL. MIC of arbekacin against 549 S. aureus isolates ranges from 0.03 to 4 microgram/mL, and MIC of vancomycin against 549 S. aureus ranges from 0.25 to 2 microgram/ mL. MIC90 of amikacin against 549 S. aureus was 32 microgram/mL, and that of gentamicin was 128 microgram/mL. MICs of amikacin and gentamicin were variable, ranging from 0.125 to 256, and otherwise arbekacin and vancomycin revealed relatively narrow range of MICs. MIC90 of arbekacin against 278 MRSA isolates & 271 MSSA were 1 & 0.5 microgram/mL, and those of vancomycin against MRSA & MSSA were 1 & 1 microgram/mL. MIC90 of amikacin against 278 MRSA & 271 MSSA isolates were 32 & 4 microgram/mL, and that of gentamicin against MRSA & MSSA isolates were 128 & 32 microgram/ mL respectively. Among 251 CNS isolates, 122 isolates were MRCNS and 129 were MSCNS. MIC50 & MIC90 of arbekacin against 251 CNS isolates were 0.25 & 2 microgram/mL, and those of vancomycin were 1 & 2 microgram/mL. MIC of arbekacin against 251 CNS isolates ranges from 0.015 to 32 microgram/mL, and that of vancomycin isolates ranges from 0.25 to 2 microgram/mL. MIC90 of arbekacin against 122 MRCNS & 129 MSCNS isolates were 2 & 0.5 microgram/mL, and those of vancomycin were 2 & 2 microgram/mL. MIC90 of amikacin against 251 CNS isolates was 32 microgram/mL, and that of gentamicin was 128 microgram/mL for CNS. MIC90 of amikacin against 122 MRCNS & 129 MSCNS isolates were 128 & 8 microgram/mL, and those of gentamicin were 256 & 32 microgram/ mL. CONCLUSION: Considering above results, arbekacin can be a useful agent against most strains of MRSA and MRCNS, which exhibit high-level resistance to amikacin and gentamicin.