Arbekacin Research Articles

Drug sensitivity and teicoplanin resistance of coagulase-negative Staphylococcus isolated from blood culture

Drug sensitivity and teicoplanin (TEIC) resistance of coagulase-negative Staphylococcus spp (CNS) isolated from blood culture in 10 years between 1992 and 2001 were investigated, and epidemiological analysis was performed using the survey of clinical backgrounds. Regarding the resistance rates of CNS to various drugs, no isolate was resistant to vancomycin (VCM), arbekacin (ABK), and linezolid (LZD), but the minimum inhibitory concentration (MIC) of TEIC was 16 micrograms/ml or higher in 10.3% of isolates. The isolates include 56 S. epidermidis strains, 1 S. capitis strain and 4 S. haemolyticus strains. As for other drugs, the minocycline (MINO) resistance rate was relatively low (6.1%), and methicillin-resistant CNS (MRCNS) accounted for 67.1%. The resistance rate was high for many drugs between 1995 and 1997. MIC50/90 of drugs considered to be anti-Staphylococcus were 1/2 microgram/ml (VCM), 1/16 microgram/ml (TEIC), 0.25/1 microgram/ml (ABK) and 1/2 microgram/ml (LZD), showing that both MIC 50 and MIC90 of ABK were the lowest. Regarding cross-resistance to TEIC, the resistant group (MIC: 16 micrograms/ml or higher) exhibited cross-resistance to all drugs excluding MINO. Particularly, 90.2% of the TEIC resistant group was MRCNS. TEIC-resistant strain was most frequently (30.8%) detected in the pediatric ward. In comparison of clinical backgrounds of the TEIC-resistant and TEIC-sensitive groups, there were no significant differences in age, use of IVH, or prognosis, but a significant difference in detection of TEIC-resistant strains was noted in patients treated with the 4 th cepharosporins and carbapenems (p < 0.01). This survey clarified the presence of TEIC-resistant CNS strains. We will continue the survey to monitor resistance conversion. Investigation of the involvement of TEIC-resistant CNS strains in hospital infection and therapeutic course is also necessary.

緑膿菌の抗MRSA活性および抗MRSA薬不活化作用について

Bacterial interactions such as methicillin-resistant Staphylococcus aureus (MRSA) growth inhibition or inactivation of anti-MRSA antibiotics by Pseudomonas aeruginosa as an indirect pathogen were tested by in vitro assay. Paired strains, P. aeruginosa and MRSA, used in this experiment were isolated from 63 respiratory samples at Juntendo University Hospital from 2002 to 2003. Growth inhibitory activities against MRSA by P. aeruginosa were tested with reversed agar plate method. Inactivation of anti-MRSA antibiotics by P. aeruginosa were assayed with disk diffusion method using agar over lay technique. Fifty-six (88.9%) out of 63 samples showed the significant MRSA growth inhibitory activity by co-existed P. aeruginosa. Anti-MRSA antibiotics such as trimetoprim-sulfamethoxazole combination (ST), arbekacin (ABK) and minocycline (MINO) except Vancomycin (VCM) and Teicoplanin (TEIC) were inactivated by the co-existed P. aeruginosa. Our data suggests that P. aeruginosa may play not only as a chronic respiratory pathogen but also as an indirect pathogen. Further, the most P. aeruginosa with anti-MRSA activity isolated respiratory sample may play as a modulator of MRSA infection.

Sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA) without effects of vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) treated successfully and safely with intravenous administration of linezolid (LZD)

Sepsis caused by methicillin-resistant <I>Staphylococcus aureus</I> (MRSA) without effects of vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) treated successfully and safely with intravenous administration of linezolid (LZD)

Efficacies of vancomycin, arbekacin, and gentamicin alone or in combination against methicillin-resistant Staphylococcus aureus in an in vitro infective endocarditis model.

We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination. Using two strains of clinically isolated methicillin-resistant Staphylococcus aureus, one GEN susceptible (GS171) and one GEN resistant (GR153), fibrin clots were prepared and suspended in the IVIEM. Antibiotics were given as boluses every 6 h (q6h), q12h, or q24h or by continuous infusion with VAN, q12h or q24h with ABK, and q8h or q24h with GEN. For combination treatment, VAN q12h plus ABK q24h and VAN q12h plus GEN q24h were given. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities were determined. The number of colonies within the fibrin clot was significantly decreased in all study groups compared with control groups (P<0.001). When VAN and ABK were administered alone, the number of colonies was significantly lower in GS171 than in GR153 by 8 h after administration (P=0.02) and was lowest in GS171 when ABK was administered q12h (P=0.01). At 72 h, ABK or VAN alone produced equivalent bacterial reductions regardless of dosing frequency and GEN resistance. In GR153, VAN plus ABK showed an additive effect till 24 h, although VAN plus GEN showed indifference. Our data suggest that ABK could be used as an alternative to VAN in GEN-resistant staphylococcal endocarditis. An additive effect was seen when VAN and ABK were used together in GEN-resistant strains until 24 h; however, further studies are warranted for the clinical application of this combination.

Application of artificial neural network modelling to identify severely ill patients whose aminoglycoside concentrations are likely to fall below therapeutic concentrations.

Identification of ICU patients whose concentrations are likely to fall below therapeutic concentrations using artificial neural network (ANN) modelling and individual patient physiologic data. Data on indicators of disease severity and some physiologic data were collected from 89 ICU patients who received arbekacin (ABK) and 61 who received amikacin (AMK). Three-layer ANN modelling and multivariate logistic regression analysis were used to predict the plasma concentrations of the aminoglycosides (ABK and AMK) in the severely ill patients. Predictive performance analysis showed that the sensitivity and specificity of ANN modelling was superior to multivariate logistic regression analysis. For accurate modelling, a predictable range should be inferred from the data structure before the analysis. Restriction of the predictable region, based on the data structure, increased predictive performance. ANN analysis was superior to multivariate logistic regression analysis in predicting which patients would have plasma concentrations lower than the minimum therapeutic concentration. To improve predictive performance, the predictable range should be inferred from the data structure before prediction. When applying ANN modelling in clinical settings, the predictive performance and predictable region should be investigated in detail to avoid the risk of harm to severely ill patients.

Efficacy and safety of arbekacin for staphylococcal infection in the NICU.

This is a retrospective study on the efficacy and safety of arbekacin (ABK), an aminoglycoside antibiotic, for acquired staphylococcal infection in the neonatal intensive care nursery. Subjects were 29 infants treated with ABK in a tertiary care neonatal center. They were 23-39 (median 28) weeks' gestation, 530-3334 (median 930) grams at birth, and 3-157 (median 17) days of age. Diagnosis of staphylococcal infection was made by clinical signs and laboratory findings. Sensitivity of the isolated organisms to ABK was tested by the microliquid dilution method. Serum ABK level was monitored to achieve the therapeutic range during the treatment. Effectiveness was defined by improving clinical signs and laboratory findings within 3 days. Effectiveness was studied in relation to type of infection and other antibiotics administered. Auditory brainstem response and serum creatinine changes were studied for ototoxicity and nephrotoxicity assessment, respectively. Twenty-seven (93.1%) cases of infection were attributed to methicillin-resistant Staphylococcus aureus (MRSA) and two (6.9%) were attributed to coagulase-negative staphylococci (CNS). The rate of in vitro sensitivity to ABK was 85.2% for MRSA and 100.0% for CNS. The overall clinical effeciveness rate was 79.3% (23/29) with no difference associated with types of infection. Combination of ABK with sulbactam/ampicillin showed greater effectiveness (100.0%) than with other antibiotics (64.3%) (P < 0.05). There was no abnormal auditory brainstem response or serum creatinine change associated with ABK treatment. ABK is an effective and safe antibiotic for the treatment of acquired staphylococcal infection in the neonatal intensive care nursery.

Pharmacokinetics and dosing of arbekacin in preterm and term newborn infants.

The objective of the present study was to determine pharmacokinetic variables and to characterize a new initial dosing regimen of arbekacin (ABK) for preterm and term newborn infants. Subjects were 40 infants treated with ABK in a tertiary care neonatal unit over a period of 18 months. At birth, the infants were 23 5/7-40 0/7 weeks and weighed 530-3428 g. Serum ABK concentration was measured at two points in a course of treatment. Data were analyzed by a one-compartment model to obtain volume of distribution (Vd) and clearance (CL) of ABK. These variables were correlated with the patients' demographic and laboratory data. The new initial dosing regimen was determined based on these data. Sixty pairs of blood samples were taken from the infants. They were divided into three groups: preterm early (PE), gestational age (GA) < 37 weeks and postnatal age (PNA) < 28 days; preterm late (PL), GA < 37 weeks and PNA >or= 28 days; and term (T), GA >or= 37 weeks and PNA < 28 days. The Vd was 0.50 +/- 0.02, 0.48 +/- 0.04, and 0.43 +/- 0.03 L/kg, and CL was 0.59 +/- 0.04, 1.12 +/- 0.10, and 0.78 +/- 0.09 mL/min per kg (mean +/- SEM) in PE, PL, and T, respectively. The new dosing regimen is 5 mg/kg every 48 h, 5 mg/kg every 24 h, and 4 mg/kg every 24 h for PE, PL, and T, respectively. With the new dosing regimen, more infants achieved serum ABK levels within the optimal range than the conventional one.

Enhancement of antimicrobial effects of various antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by combination with fosfomycin.

The present study was designed to evaluate the efficacy of fosfomycin used in combination with drugs that were found to be less effective against methicillin-resistant Staphylococcus aureus (MRSA). Twelve different antibiotics were tested against 32 strains of MRSA isolated from the wounds of burn patients admitted to the Burn Unit at Tokyo Women's Medical University Hospital. These antibiotics - fosfomycin (FOM), flomoxef sodium (FMOX), imipenem (IPM), cefotiam (CTM), cefmetazole (CMZ), ampicillin (ABPC), sulbactam/cefoperazone (SBT/CPZ), minocycline (MINO), ofloxacin (OFLX), and panipenem (PAPM) - were used either alone or in combination. Arbekacin (ABK) and vancomycin (VCM) were used for comparing efficacy in controlling bacterial growth. While both ABK and VCM were, as expected, found to be effective in suppressing in vitro bacterial growth, all ten other agents when used alone were found to be ineffective. In contrast, these agents, when used in combination with FOM, showed remarkable efficacy against all strains of MRSA tested. Based upon the in vitro findings, it is suggested that FOM, in combination with other antimicrobial agents, such as IPM, PAPM, CMZ, and SBT/CPZ may be used instead of ABK and/or VCM to curtail the emergence of Staphylococcus aureus strains that are resistant to these latter two drugs.

Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penisillin-resistant Streptococcus pneumoniae between 1998 and 2000 in the Kinki district

Kinki Infection Working Group made an annual (1998-2000) comparative study of an epidemiological investigation for Staphylococcus aureus and Streptococcus pneumoniae in the Kinki district. The number of S. aureus and methicillin-resistant S. aureus (MRSA) isolated decreased for three years, but the isolation frequencies of MRSA has not changed which was approximately 60%. All strains of MRSA were not resistant to vancomysin (VCM) and teicoplanin (TEIC), and the frequencies of resistance to sulfamethoxazole-trimethoprim (ST) and arbekacin (ABK) were 0.1 to 0.7% and 1.9 to 3.1%, respectively. On the other hand, the number of S. aureus and penicillin-resistant S. pneumoniae (PRSP) isolated did not show a consistent tendency, but the isolation frequencies of PRSP has increased for three years. All strains of PRSP were sensitive to vancomycin (VCM), but the frequencies of resistance to cefaclor and other some antibiotics have increased.

Survey of methicillin-resistant coagulase-negative staphylococci isolated from the fingers of nursing students.

To clarify the state of methicillin-resistant coagulase-negative staphylococci (MRCNS) contamination in the hospital environment, we compared MRCNS isolated from the fingers of 40 nursing students who had not yet experienced clinical practice and 40 who had just completed clinical practice in the hospital. Fourteen MRCNS strains were detected in 13 students (32.5%) after clinical practice; Staphylococcus epidermidis in 9 students, Staphylococcus haemolyticus in 3, and Staphylococcus saprophyticus in 2. Drug sensitivity tests were performed, and the minimum inhibitory concentration (MIC) of penicillin-G (PCG) was more than 2 microg/ml in all strains, and that of ampicillin (ABPC) was more than 16 microg/ml in many strains. Only a few strains showed high MIC values for the other drugs tested. However, some Staphylococcus haemolyticus strains showed high MIC values for cefazolin (CEZ), arbekacin (ABK), gentamicin (GM), ofloxacin (OFLX), or imipenem (IPM). In all strains, the mecA gene was detected by polymerase chain reaction (PCR), and penicillin binding protein 2' (PBP2') was detected by the latex agglutination method. Methicillin-resistant Staphylococcus epidermidis (MRSE) isolated from the fingers of nursing students was compared with that isolated from blood culture specimens by arbitrarily primed (AP)-PCR analysis. The patterns obtained were different, a finding which excluded the presence of cross-infection. The present results show that basic preventive measures for cross-infection should be considered in the future, using such genetic analysis methods, so that MRCNS may not cause hospital infection.

Methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections in the cornea.

To describe the incidence and clinical management of corneal infections with methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). The incidence of methicillin-resistant Staphylococcus (MRS) at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, was reviewed during the 5-year period from January 1996 to December 2000. Clinical aspects of MRS colonization or infection in the eye were investigated. Methicillin-resistant S. aureus or MRSE was detected from 30 eyes with ocular diseases; post-keratoplasty (11 eyes), ocular surface disorders without operation (9 eyes), and others (10 eyes). Among the 30 eyes, 12 manifested keratitis. Eight cases (8 eyes) occurred after keratoplasty, including four postoperative cases in patients with Stevens-Johnson syndrome, and two bilateral cases (4 eyes) in patients with acute-phase Stevens-Johnson syndrome. The degree of MRS keratitis was classified into 4 groups: asymptomatic carrier or conjunctivitis, intraepithelial infiltrations, superficial keratitis, and severe keratitis leading to corneal perforation. All cases of keratitis were treated successfully with topical ofloxacin (OFLX), vancomycin (VCM), or arbekacin (ABK). Factors associated with ocular MRS colonization were long-term use of antibiotics and/or steroids, and hospitalization. Patients who had undergone keratoplasty or who had Stevens-Johnson syndrome were at increased risk of MRS keratitis. Superficial stromal infiltrations, minimal melting, and minimal stromal scarring are characteristic of MRS keratitis. Therapy for MRS keratitis is summarized. Ofloxacin, VCM, and ABK are effective in the treatment of MRS keratitis. Vancomycin eye ointment is effective as the final choice in serious cases.

Double stage activity in aminoglycoside antibiotics.

Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKB also retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM, paromomycin], NM retained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTM and istamycin B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others. Streptomyces lividans TK21 containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.

Specificity of 4'''-acetylation by an aminoglycoside-modifying enzyme in arbekacin-resistant strains of methicillin-resistant Staphylococcus aureus.

Four arbekacin (ABK)-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were studied regarding their mechanism of aminoglycoside-resistance. Metabolites of amikacin (AMK) and gentamicin(GM) were obtained by reaction with excess amounts of crude enzyme preparation extracted from the ABK-resistant MRSA strains. Then the metabolites were then isolated and analyzed by means of 1H, 13C-nuclear magnetic resonance. The AMK-modification was 4'''-N-acetylation. However, the site of GM-acetylation may be 6'-N-position by these strains.

Blepharismin produced by a protozoan Blepharisma functions as an antibiotic effective against methicillin-resistant Staphylococcus aureus

A ciliated protozoan, Blepharisma japonicum, produces a photosensitive red pigment, blepharismin (BLR). This study showed that the pigment inhibits the growth of Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) resistant to arbekacin (ABK), which is the most effective aminoglycoside antibiotic against MRSA and used world wide. Although the minimum inhibitory concentration (MIC) of BLR to the ABK-resistant MRSA strain was 6.25 μg/ml in dark, it was decreased to 1.25 μg/ml by irradiation with white light of 65 W/m 2 for 30 min, suggesting that the antibacterial activity of BLR is photoactivated. Our findings suggested that the antibacterial activity of BLR in dark is due to inhibition of protein synthesis. In addition, we found that BLR is bactericidal and enhances synergistically the antibacterial activity of ABK.

Investigation of nosocomial infection caused by arbekacin-resistant, methicillin-resistant Staphylococcus aureus

An outbreak of coagulase VII-producing, arbekacin (ABK)-resistant, methicillin-resistant Staphylococcus aureus (MRSA) occurred between September 1994 and December 1995, involving five different wards. Twenty-one patients developed skin, wound, drainage, or respiratory tract colonization with coagulase VII-producing, (ABK)-resistant MRSA. Phenotypic characteristics (production of enterotoxin and TSST-1, antimicrobial susceptibility) and molecular-typing procedure (plasmid DNA profile, pulsed-field gel electrophoresis [PFGE] and arbitrarily primed polymerase chain reaction [AP-PCR] of chromosomal DNA) in isolated strains were compared. Plasmid analysis identified four different profiles and 19 of 22 strains recovered had identical patterns. PFGE of chromosomal DNA identified three different subtypes and 18 (81.8%) isolates shared the same subtype. AP-PCR also demonstrated that most strains had the same phenotypic characteristics. Although traditional epidemiological methods; for example, coagulase typing, plays a central role in hospital infection control, combination of plasmid DNA profile, AP-PCR, and PFGE may prove to be a particularly informative means of tracking the nosocomial spread of MRSA.

Nationwide survey of susceptibilities of clinical isolates to antibacterial agents in 1992

This study was conducted to investigate susceptibilities of clinical isolates to imipenem (IPM) and other antibacterial agents in 144 hospital laboratories throughout Japan from September to December of 1992. In this study, the isolates were identified and susceptibility tests were performed at individual laboratories. The susceptibility tests were performed using the disk dilution method recommended by NCCLS. S. aureus (including MRSA) strains were highly susceptible to arbekacin (ABK) and netilmicin (NTL). S. pneumoniae and H. influenzae were susceptible to most of the agents tested. E. faecalis were highly susceptible to penicillins and imipenem (IPM). P. aeruginosa showed high susceptibility to ceftazidime (CAZ), IPM and amikacin (AMK). Annual changes in antimicrobial susceptibility patterns over 5 years (1988-1992) were examined. The frequency of sensitive strains of S. aureus to methicillin (DMPPC) has slightly increased from 1991 to 1992. A moderate increases of PCG-insensitive S. pneumoniae was observed. B. fragilis group showed a slight increase in sensitivity to minocycline (MINO) but no yearly changes in IPM sensitivity was observed.

Antibacterial activity and nephrotoxicity of two novel 2″-amino derivatives of arbekacin

The antibacterial activity of 2″-amino-2″-deoxyarbekacin (AmABK) and 2″-amino-5,2″-dideoxy-5-epiaminoarbekacin (Am2ABK) was comparable to, or slightly less than, that of arbekacin (ABK) against gram-positive and gram-negative bacteria, including 60 stock cultures and 50 clinical isolates of Pseudomonas aeruginosa, but more potent against 31 isolates of MRSA possessing an aminoglycoside-modifying enzyme APH(2″)/AAC(6'). AmABK and Am2ABK showed in vivo activity which paralleled in vitro MICs, and were less toxic than ABK in acute toxicity in mice and nephrotoxicity in rats. These results indicate that the 2″-amino group introduced to ABK confers high stabilization to the aminoglycoside-modifying enzymes, while reducing acute and renal toxicities. l infect Chemother 1996;2:84-89.

Synthesis of 5-deoxy-5-epifluoro derivatives of arbekacin, amikacin, and 1- N-[( S)-4-amino-2-hydroxybutanoyl]tobramycin (study on structure — toxicity relationships)

As part of a study on fluorination—toxicity relationships for aminoglycoside antibiotics, 5,3′-dideoxy-5-epifluorokanamycin B ( 10), 5,3′,4′-trideoxy-5-epifluorokanamycin B ( 11), 1- N-[( S)-4-amino-2-hydroxybutanoyl]-5-deoxy-5-epifluorotobramycin ( 19), 5-deoxy-5-epifluoroarbekacin ( 20), and 5-deoxy-5-epifluoroamikacin ( 21) have been prepared. The acute toxicities of these three 5-deoxy-5-epifluoro compounds showed values almost identical or similar to those for arbekacin (ABK) and amikacin ( 15), making a sharp contrast with the toxicities of the corresponding 5-deoxy-5-fluoro derivatives. This fact is explained on the basis of basicity changes (retention for the 5-epifluoro derivatives and reduction for the 5-fluoro derivatives) at the H 2N-3 groups of the fluorinated compounds compared to the parent compounds; this hypothesis was substantiated by the p Ka values at the H 3N +-1, 3 groups (determined by the shift changes depending on pD values at C-2 and C-4, 6 in their 13C NMR spectra) of 2,5-dideoxy-5-epifluorostreptamine ( 23) and 2,5-dideoxy-5-fluorostreptamine ( 24), chosen as model compounds, and 2-deoxystreptamine (DST).

Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1991)

Isolated bacteria from respiratory tract infections were collected since 1981 in cooperation with institutions located throughout Japan, and have been investigated for their sensitivities to various antibacterial agents and antibiotics and reported by IKEMOTO, et al. Relationships between these isolates and backgrounds of the patients were also studied each year. These results are discussed in detail in this report. In 20 institutions around the entire Japan from October 1991 to September 1992, 631 strains of bacteria were isolated mainly from sputa of 529 patients with respiratory tract infections and tentatively determined to be etiological agents. MICs of various antibacterial agents and antibiotics against 96 strains of Staphylococcus aureus, 112 strains of Streptococcus pneumoniae, 111 strains of Haemophilus influenzae, 114 strains of Pseudomonas aeruginosa (non-mucoid), 41 strains of Moraxella subgenus Branhamella catarrhalis, 39 strains of Pseudomonas aeruginosa (mucoid), Klebsiella pneumoniae and some others, were determined, and the drug sensitivities of these strains were determined except for the strains that had been killed during transportation: 1. S. aureus. S. aureus strains for which MICs of methicillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 58.3% and the frequency of the drug resistant bacteria increased over previous year's 42.5%. As shown by the MICs, arbekacin was active as vancomycin against all the strains on S. aureus. 2. S. pneumoniae: Benzylpenicillin among the penicillins showed a potent activity against S. pneumoniae. Cefuzonam, cefmenoxime, cefozopran and cefotaxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; a penem antibiotic, showed the most potent activity with MIC80 of 0.03 micrograms/ml. 3. H. influenzae: Activities of all drugs were excellent against H. influenzae strains tested. Ampicillin showed MIC80 of 1 micrograms/ml against H. influenzae. Cefuzonam showed the most potent activity among cephems, it completely killed all bacteria at MIC 0.06 micrograms/ml. Cefotaxime and cefmenoxime showed next most potent activities with MIC80s of 0.06 micrograms/ml. The antimicrobial activity of ofloxacin was equivalent to those of cephems. 4. P. aeruginosa (mucoid). Ciprofloxacin and tobramycin showed the most potent activities against P. aeruginosa (mucoid), and their MIC80s were 4 micrograms/ml. 5. P. aeruginosa (non-mucoid): Similarly, ciprofloxacin and tobramycin showed the most potent activities against P. aeruginosa (non-mucoid) with MIC80 of 2 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested showed lower activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae: The activities of all drugs except for penicillins were very high against K. pneumoniae.(ABSTRACT TRUNCATED AT 400 WORDS)

A possible immunomodulating activity of arbekacin (ABK), a newly synthesized antibiotic against methicillin-resistant Staphylococcus aureus (MRSA)

Arbekacin (ABK) is a newly developed aminoglycoside in Japan which can cause bactericidal effects on methicillin-resistant Staphylococcus aureus (MRSA). However, details of the mechanism on effective antibacterial activity of this drug in host patients has not been completely elucidated. We studied the modulating effects on some functional activities of immunocompetent cells in in vitro and in vivo mouse experimental systems. 1. (i) ABK stimulated the phagocytic activity against S. aureus into mouse phagocytic cells in a dose-dependent manner. 2. (ii) ABK enhanced oxygen radical generation with chemiluminescence in mouse phagocytic cells. 3. (iii) ABK exhibited a stimulatory effect on interleukin 1α release from mouse adherent cells. 4. (iv) Injection with ABK into mice showed an adjuvant activity which stimulated antibody production against sheep red blood cells and S. aureus. These experimental results indicate the possibility that ABK has not only a direct antibacterial activity but also a modulating activity for immunocompetent cells to enhance host defense against S. aureus infection.