Antibacterial activities and PK/PD parameters of aminoglycosides against recent clinical isolates of gram-negative rods

We examined antibacterial activities and PK/PD parameters of six kinds of aminoglycosides against seven bacterial species of clinical isolates in 2001. Aminoglycoseides examined were gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), netilmicin (NTL), and isepamicin (ISP), and bacterial isolates used were each 50 strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus spp., Serratia marcescens and Pseudomonas aeruginosa. All aminoglycosides showed good activities with low MICs against 6 species of Enterobacteriacea except S. marcescens. Eight strains (3.2%) among them were resistant to one or more aminoglycosides. Resistance to multiple aminoglycosides were detected in 16 strains (32%) of S. marcescens, among which 13 strains were resistant to AMK but susceptible to ISP. Three (6%) strains of P. aeruginosa were resistant to multiple drugs, one of which was resistant to all six aminoglycosides, and others were moderately susceptible to AMK and ISP, and susceptible to GM, AMK and ISP. Using a ratio of peak serum concentration to MIC90 (Cmax/MIC90) or a ratio of area under the curve to MIC90 (AUC/MIC90) as a pharmacokinetic and pharmacodynamic (PK/PD) parameter, we estimated the efficacy of the drug. An excellent effect of ISP, which was injected intramuscularly or intravenously at a dose of 400 mg, was expected for strains of Enterobacteriacea except S. marcescens. The Cmax/MIC90 ratios for S. marcescens were comparably higher in GM and ISP and that for P. aeruginosa were rather high in TOB when compared to other aminoglycosides. Another PK/PD parameter, AUC/MIC90 ratio, was high enough in NTL and ISP for Enterobacteriacea, suggesting good efficacy of these drugs. The (AUC/MIC90) ratios for S. marcescens were comparably high in GM and ISP, and that for P. aeruginosa were high in TOB, DKB, and ISP.     

Antimicrobial activities of gentamicin against fresh clinical isolates

Antimicrobial activities of gentamicin (GM), compared with activities of other aminoglycosides (AGs) and beta-lactam antibiotics, were studied against clinical isolates obtained during a period of July-December 1989. 1. GM-resistant strains were noted in 24% of Staphylococcus aureus, 12% of Enterobacter spp., 24% of Serratia marcescens, 7% of Morganella morganii and 26% of Pseudomonas aeruginosa, but no GM-resistant strains were observed among isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris. 2. A majority of GM-resistant strains of S. aureus were methicillin-resistant S. aureus (MRSA) and a large number of GM-resistant strains of Enterobacter spp. was also resistant to new quinolones. GM showed, however, strong antimicrobial activities against new quinolones-resistant strains of S. marcescens, M. morganii and P. aeruginosa. 3. Among all the isolates tested of S. marcescens, 24% were GM-resistant, 72% were tobramycin (TOB)-resistant, 86% were dibekacin (DKB)-resistant and 64% were amikacin (AMK)-resistant, hence the incidence of GM-resistant strains was the lowest. This tendency was also observed with P. vulgaris. However, among P. aeruginosa, 26% were GM-resistant, 14% TOB-resistant, 18% DKB-resistant and 22% AMK-resistant, thus the incidence rate for GM-resistance was somewhat higher. These results suggest that different AGs-modification enzymes were produced by various clinical isolates under the present condition. 4. Comparing the ratio of GM-resistant strains in the present study with those in 1980 and 1983, the ratio increased among S. aureus, while decreases were observed among Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, indicating that a unilateral tendency of increases in GM-resistant strains did not exist among clinical isolates over the years.     

木犀草素与抗菌药体外联用抗耐甲氧西林金葡菌的作用研究

目的：考察木犀草素与抗菌药体外联用抗耐甲氧西林金葡菌的作用。方法：采用倍比稀释法测定药物最小抑菌浓度;通过双纸片法、微量棋盘稀释法和时间-杀菌曲线法等实验,评价木犀草素与抗菌药联用对耐甲氧西林金葡菌的抑菌效果。结果：木犀草素对受试MRSA菌株均有抑制作用,最小抑菌浓度为32～128 mg.L-1;其与某些喹诺酮类和氨基糖苷类抗菌药联用时的部分抑菌浓度指数小于或等于0.5,呈现协同抑菌作用,且联用时抗菌药用量较单用时明显减少;时间-杀菌曲线显示,其与抗菌药联用在12和24 h时的协同抑菌效果最好。结论：木犀草素具良好的抗耐甲氧西林金葡菌活性,并与喹诺酮类和氨基糖苷类抗菌药联用具协同抑菌作用。     

Antibacterial activity of gentamicin against clinical isolates in pediatrics

Antibacterial activity of gentamicin (GM), along with activities of other aminoglycosides and beta-lactams, was studied against clinical isolates collected from pediatric patients during a period of May 1986-April 1987. 1. GM-resistance was noted in 22% of Staphylococcus aureus, 6% of Proteus vulgaris, 8% of Morganella morganii, 40% of Providencia spp., 6% of Enterobacter spp., 14% of Serratia marcescens, and 14% of Pseudomonas aeruginosa isolates. No GM-resistance was observed with isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. 2. The antibacterial activity of GM against clinical isolates from pediatric patients was found to be comparable to its activity against clinical isolates from adults studied at the same time. 3. The majority of GM-resistant strains of S. aureus were MCRSA, and the GM-resistant strains of S. marcescens and P. aeruginosa were found also to be resistant to multiple drugs. 4. GM-resistant strains were found at relatively high rates (14-22%) in S. aureus, S. marcescens and P. aeruginosa. These rates did not increase compared to the rates observed in the first half of the 1980's. 5. GM was considered to have poor antibacterial activity against genus Providencia. It is concluded from above results that GM still maintains effective antibacterial activity against many of causative organisms of infections in both adults and children.     

国产米诺环素对耐甲氧西林金葡球菌的体外抗菌活性观察

用琼脂稀释法进行国产米诺环素对１０４株耐甲氧西林金葡球菌（ＭＲＳＡ）和１２０株甲氧西林敏感金葡球菌（ＭＳＳＡ）的抗菌活性研究，并与日本产米诺环素等进行了抗菌作用比较。结果表明国产米诺环素对ＭＲＳＡ和ＭＳＳＡ的抑菌效果，与日本产米诺环素基本一致。对ＭＲＳＡ的ＭＩＣ５０和ＭＩＣ９０前者分别为２和８ｍｇ／Ｌ，而后者分别为２和４ｍｇ／Ｌ。两者对ＭＳＳＡ的ＭＩＣ５０和ＭＩＣ９０均为０．５和４ｍｇ／Ｌ。国产米诺环素与其它６种抗生素比较，除去甲万古霉素外，其对ＭＲＳＡ和ＭＳＳＡ的抗菌效果，均优于头孢唑林等抗生素     

In vitro combination effect of pazufloxacin with various antibiotics against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

The in vitro combination effects of pazufloxacin (PZFX) with various antibiotics were investigated by the checkerboard dilution method using piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefozoprane (CZOP), imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP), amikacin (AMK) and isepamicin (ISP) for clinical isolates of 27 Pseudomonas aeruginosa strains, vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) for clinical isolates of methicillin-resistant 26 Staphylococcus aureus (MRSA) strains, respectively. The following results were obtained. 1. For 27 P. aeruginosa strains, the synergistic effects were observed with the combination of PZFX and CAZ or MEPM (11.1%: 3 strains), and PZFX and CZOP or PAPM/BP (3.7%: 1 strain), respectively. The additive and synergistic effects of PZFX were observed with the combination in all beta-lactams tested in the strains more than 50%. No antagonistic effect was observed. The additive effects were also observed with the combination of PZFX and AMK or ISP in the strains more than 50% of the test strains and no antagonistic effect was observed. 2. For 26 MRSA strains, no antagonistic effect was observed with the combination of all antibiotics tested. The indifference was observed with the combination of PZFX and VCM or ABK in the strains more than 60%, and the additive effects were observed with the combination of TEIC in the strains more than 80%. In conclusion, no antagonistic effect was observed in PZFX with the combination of beta-lactams and anti-MRSA agents, suggesting that the combination therapy of PZFX with these antibiotics would be possible to use for the infections caused by P. aeruginosa and MRSA.     

In vitro interaction of tazobactam/piperacillin combined with aminoglycosides against Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli AND Staphylococcus aureus

The in vitro combination effect of tazobactam/piperacillin (TAZ/PIPC) with aminoglycosides (amikacin (AMK) and isepamicin (ISP)) were investigated by the checkerboard dilution method against PIPC-resistant and TAZ/PIPC-susceptible Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Methicillin-sensitive Staphylococcus aureus (MSSA). The following results were obtained. 1. The combination of TAZ/PIPC with AMK showed synergistic effect for 66.7% of P. aeruginosa and 9.1% of K. pneumoniae and additive effect for 76.9% of E. coli and 74.1% of MSSA. The antagonistic effect of TAZ/PIPC with AMK was not demonstrated for all tested strains. 2. The combination of TAZ/PIPC with ISP showed synergistic effect for 61.9% of P. aeruginosa and 22.7% of K. pneumoniae and additive effect for 84.6% of E. coli and 66.7% of MSSA. The antagonistic effect of TAZ/PIPC with ISP was not demonstrated for all tested strains. In conclusion, these results suggest that the combination therapies of TAZ/PIPC with aminoglycosides are useful for the clinical treatment of sepsis caused by above four species.     

Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. I. Effect of sulbactam against beta-lactams resistant strains and in vitro combined effect of sulbactam/cefoperazone with each of piperacillin, latamoxef, ceftazidime, fosfomycin and doxycycline

We evaluated relationships between production of beta-lactamase and their resistances to beta-lactams, effect of sulbactam (SBT), a beta-lactamase inhibitor, against beta-lactam resistant strains, and combined effect of sulbactam/cefoperazone (SBT/CPZ) with other antibiotics against multi-resistant strains. Through these studies, we obtained the following results. 1. Most of the strains resistant to beta-lactams were beta-lactamase producers. 2. Relationships between the production of beta-lactamase and their resistances to beta-lactams indicate that their resistances generally were the highest in producers of both penicillinase (PCase) and cephalosporinase (CEPase), moderate in producers of either PCase or CEPase, and the lowest in beta-lactamase non-producers. Most of highly-resistant strains of MRSA appeared to be beta-lactamase non-producers though some exceptions were observed among methicillin-resistant Staphylococcus aureus (MRSA), Serratia marcescens and Pseudomonas aeruginosa. 3. SBT showed good effect against PCase producers, moderate effect against producers of both PCase and CEPase, little effect against CEPase producers, and no effect against beta-lactamase non-producers. 4. Results of combined effect of SBT/CPZ with other antibiotics indicated that good synergism was obtained by combining SBT/CPZ with fosfomycin (FOM) or piperacillin against multi-resistant strains of Proteus spp., Enterobacter cloacae, and S. marcescens, by combining SBT/CPZ with ceftazidime (CAZ) or FOM in methicillin-sensitive S. aureus and by combining SBT/CPZ with CAZ in P. aeruginosa. 5. Better synergism was obtained with the higher concentrations of antibiotics.     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

Comparison of the antibacterial activity of amikacin (BB-K8) with other aminoglycosides against pathogens recently isolated from clinical materials (author's transl) ]

We determined the antibacterial activity of amikacin against 1,277 strains of pathogenic bacteria isolated from clinical materials during 1974, including beta hemolytic streptococci, pneumococci, enterococci, Staphylococcus aureus, Staph. epidermidis, Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, Proteus morganii and Pseudomonas aeruginosa, and compared the minimum inhibitory concentration (MIC) of this drug with gentamicin, dibekacin, tobramycin and kanamycin. 1)Antibacterial activity of amikacin against beta hemolytic streptococci, pneumococci and enterococci was as weak as the other four aminoglycosides, but against Staph. aureus, Staph. epidermidis, various groups of Enterobacteriaceae and Pseudomonas aeruginosa showed amikacin the good antibacterial activity as gentamicin, dibedacin and tobramycin, and also showed the good activity against kanamycin resistant strains. 2) Amikacin has the similar antibacterial spectrum as gentamicin, dibekacin or tobramycin, but its antibacterial activity is generally weakest among these four drugs. 3) On many strains tested the cross resistance is observed between amikacin and one of gentamicin, dibekacin and tobramycin, but several strains of Proteus morganii and Pseudomonas aeruginosa which have rather large MIC against gentamicin, dibekacin or tobramycin showed rather small MIC against amikacin.     

Isepamicin与六种氨基糖苷类体外抗菌活性研究

本文比较fsepamicin(ISP)、庆大霉素(GM)、地贝卡星(DKB)、乙基西索米星(NTL)、妥布霉素(TOB)、西索米星(SISO)与阿米卡星(AMK)的体外抗菌活性。金葡菌产酶株对上述抗生素的敏感性显较不产酶株为差,以ISP、NTL对金葡菌产酶株的作用最强。其平均MIC值分别为1.85和2.12mg/L;对革兰氏阴性杆菌的作用则以ISP和AMK为强。以ISP对各种细菌的MIC值最低0.32～3.39mg/L。TOB、GM、SISO、NTL与DKB对多数革兰氏阴性杆菌的作用相似,五者之间有很大程度交叉耐药。所测611株革兰氏阴性杆菌中对一种以上药物耐药者312株,占51％;其中对ISP和AMK仍敏感者分别为90.4％和91.7％,而对NTl、GM、TOB、DKB敏感者仅15～18％,本文讨论了细菌对氨基糖苷类的耐药机理及其临床意义。     

Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

The incidence of methicillin resistant S. aureus strains in clinical specimens in relation to their beta-lactamase producing and multiple-drug resistance properties in Addis Abeba

From December 1987 to July 1988, a total of 17,142 clinical specimens were examined at the National Research Institute of Health (NRIH), Addis Abeba, to determine the incidence of methicillin resistant S. aureus (MRSA) strains. Coagulase positive Staphylococcus spp. were isolated from 355 specimens. Two hundred and forty-nine 249 (70%) isolates were tested for methicillin resistance by minimum inhibition concentration method (MIC) of which 76 (30.5%) were found to be MRSA and 173 (69.5%) were methicillin sensitive S. aureus (MSSA) strains. The presence of beta-lactamase production was determined in the 355 S. aureus isolates using the rapid Iodometric and Nitrocefin methods and 252 (71%) isolates were found to be beta-lactamase procedures. Furthermore, 47 (62%) of the 76 MRSA isolates and 140 (81%) of the 173 MSSA isolates were beta-lactamase positive strains. The sensitivity pattern of all the S. aureus isolates against 11 common drugs indicated that the majority (80%) of the MRSA strains were multipledrug resistant while 4 (8%) were not resistant to any of the drugs tested. Among the antibiotics, vancomysin and clindamycin were effective against all S. aureus isolates. It was also found that 41 (54%) of the MRSA strains were both betalactamase producers and multiple-drug resistant isolates; of the latter, 36 (87.8%), strains were isolated from pus specimens of patients with post-operative wound infections. The results of this study show that MRSA strains are quite prevalent among specimens referred to the NRIH.     

In vitro activity of clinafloxacin against fluoroquinolone resistant Spanish clinical isolates.

The in vitro activity of clinafloxacin against 162 ciprofloxacin-resistant clinical isolates was determined. Isolates were selected when their MIC to ciprofloxacin was 2 mg/l (intermediate) or > 2 mg/l (resistant). The following strains were tested: 61 Escherichia coli, 12 Klebsiella pneumoniae, 7 Proteus mirabilis, 21 Serratia marcescens, 4 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 21 Staphylococcus. aureus (resistant to methicillin) and 15 Enterococcus spp. Clinafloxacin, ciprofloxacin, ofloxacin and norfloxacin activities were evaluated by agar dilution using Müeller-Hinton agar according to NCCLS recommendations. Of the 162 isolates, 16 (9.8%) were intermediate and 146 (90.1%) resistant to ciprofloxacin. 95 of the 162 strains (58.6%) were susceptible, 27 (16.7%) intermediately susceptible, and 40 strains (24.7%) were resistant to clinafloxacin. The percentage susceptible to clinafloxacin was 65.6% for E. coli, 75% for K. pneumoniae, 71.4% for P. mirabilis, 28.6% for S. marcescens, 75% for E. cloacae, 33.3% for P. aeruginosa, 90.5% for S. aureus and 40% for Enterococcus spp. Clinafloxacin was active against 58.6% of the ciprofloxacin-resistant clinical isolates tested. It was particularly active against S. aureus strains resistant to both ciprofloxacin and methicillin.     

Antibacterial activities of piperacillin for several resistant strains from respiratory infections--in reference to MRSA, PRSP, BLNAR and P. aeruginosa

We investigated antibacterial activities of piperacillin (PIPC) for several resistant strains of bacteria isolated from patients with respiratory infections from 1998 to 1999 in comparison with reference drugs and obtained the following results: 1. The majority of methicillin resistant strains of Staphylococcus aureus (MRSA) showed high resistance to beta-lactam antibiotics including PIPC. 2. MIC90 of PIPC was 1 and 4 micrograms/ml for penicillin intermediate and penicillin resistant strains of Streptococcus pneumoniae (PISP/PRSP), respectively. 3. MIC90 of PIPC was 0.25 microgram/ml for beta-lactamase negative ampicillin resistant strains of Haemophilus influenzae (BLNAR), showing higher antibacterial activity than the reference drugs. 4. PIPC exhibited the MICs of 8 micrograms/ml or less in 19 out of 40 IPM resistant (MIC > or = 16 micrograms/ml) strains of Pseudomonas aeruginosa. From these results, PIPC is proved to possess extremely favorable antibacterial activities for BLNAR, and it was suggested that PIPC might be a drug of choice even for PISP/PRSP and IPM resistant strains of P. aeruginosa.     

Antibacterial activities of sisomicin against fresh clinical isolates]

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.     

山西临汾地区耐甲氧西林金黄色葡萄球菌临床分布及耐药性分析

目的了解山西临汾地区临床标本分离出的耐甲氧西林金黄色葡萄球菌(MRSA)临床分布及对常用抗菌药物的耐药性,为临床合理应用抗生素提供参考依据。方法 API系统鉴定细菌,用MIC法ATBSTAPH5板条进行药物敏感分析,MRSA用头孢西丁纸片扩散法(K-B法)筛选,用WHONET 5.4软件进行统计学分析。结果共检出金黄色葡萄球菌137株,其中MRSA 59株,MRSA的平均检出率为30.1%。MRSA主要分布在重症监护病房(35.6%)和神经外科(18.6%)。感染标本以痰(59.3%)、伤口分泌物(32.2%)为主。MRSA对β-内酰胺类、大环内酯类、喹诺酮类、氨基糖苷类、林可霉素、四环素的耐药率均>80%,但对复方磺胺甲(口恶)唑敏感率高(84.8%)。未发现对万古霉素、替考拉宁、达福普汀和呋喃妥因耐药的菌株。结论临汾地区金黄色葡萄球菌中MRSA分离率低,MRSA耐药严重且呈多重耐药。     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.     

In vitro interaction of piperacillin and imipenem/cilastatin combined with aminoglycosides against Pseudomonas aeruginosa

The in vitro interactions of piperacillin (PIPC) and imipenem/cilastatin (IPM/CS) combined with 5 kinds of aminoglycosides (gentamicin, tobramycin, amikacin (AMK), isepamicin and netilmicin) were investigated against IPM/CS-susceptible (MIC of IPM/CS was < or = 3.13 micrograms/ml) and IPM/CS-resistant (MIC of IPM/CS was > or = 12.5 micrograms/ml) Pseudomonas aeruginosa. The following results were obtained. 1. In the checkerboard dilution studies, the combinations of PIPC with aminoglycosides showed synergistic effect for more than 50% of the each 54 strains of IPM/CS-susceptible and IPM/CS-resistant P. aeruginosa. The synergistic/additive effects of PIPC with aminoglycosides were demonstrated for all tested strains. 2. In the checkerboard dilution studies, the combinations of IPM/CS with aminoglycosides showed no antagonism against any strains. The synergistic effects of IPM/CS with aminoglycosides were demonstrated for 0 to 14.8%, and these values were smaller than the combinations of PIPC with aminoglycosides. 3. Corresponding to the results of checkerboard dilution studies, the combination of PIPC with AMK was more effective than the combination of IPM/CS with AMK on the killing curve for IPM-resistant P. aeruginosa. In conclusion, PIPC showed the synergistic effects in combinations with aminoglycosides against IPM/CS-resistant P. aeruginosa. These results suggest that the combination therapies of PIPC with aminoglycosides are useful for the clinical treatment of serious infections due to P. aeruginosa.     

Study of clinical bacteriological efficacy in a cefmenoxime ototopical solution

One percent cefmenoxime (CMX) ototopical solution was administered to 302 patients with purulent otitis media and acute diffuse external otitis in open study fashion, and to 216 patients with purulent otitis media in double blind condition. From among the total of 518 cases various bacteria were detected, except 22 of negative detection after incubation and 3 of impossible determination. The main bacteria detected from the above 493 cases were S. aureus (242 strains = 49.1%), P. aeruginosa (105 strains = 21.3%), S. epidermidis (67 strains = 13.6%), Proteus spp. (indole positive) (31 strains = 6.3%) and P. mirabilis (24 strains = 4.9%) as well as anaerobic bacteria (26 strains = 5.3%). MIC of CMX against those bacteria detected was evaluated at 10(8) CFU/ml and 10(6) CFU/ml, respectively, up to the concentration of 800 micrograms/ml, with MIC of cefazolin (CEZ), chloramphenicol (CP) and fradiomycin (FRM) as the references. With respect to the antibacterial action of CMX against S. aureus, MIC50 of CMX was inferior to that of CEZ by 4-fold, but its MIC80 and MIC90 are almost equivalent to those of CEZ. These results were obtained because there existed relatively few CMX highly resistant strains, while more than 20% strains are said to resist cephem antibiotics. As far as MIC of CMX against P. aeruginosa was concerned, the MIC reached its peak with 100 micrograms/ml at the concentration of 10(8) CFU/ml and with 25 micrograms/ml at 10(6) CFU/ml, respectively, which indicated the real antibacterial value of CMX against P. aeruginosa. However, the strains which showed higher MIC of greater than 800 micrograms/ml were rather few, that is, only 8 out of 105 (7.6%). Antibacterial action of CMX against Streptococcus (except Enterococcus), GNR from intestinal bacteria and anaerobic bacteria was favorable, and the stable and strong antibacterial action was shown against C. freundii, Enterobacter spp., S. marcescens and Proteus spp. (indole positive) which produce chromosome mediated beta-lactamase. On the other hand, the antibacterial action of CMX against GNF-GNR except P. aeruginosa was unfavorable for P. cepacia, P. putida and A. xylosoxidans, but relatively favorable for A. calcoaceticus. As a result of MIC evaluation of reference drugs, S. aureus was resistant to CEZ, and Proteus spp. (indole-positive) was resistant to CP, while FRM was highly resisted by almost all strains of bacteria. However, the resistance rate of S. aureus to CP was relatively low, that is, as low as 16.1%.(ABSTRACT TRUNCATED AT 400 WORDS)