In vitro activity of garenoxacin against recent clinical isolates of Chlamydia pneumoniae

The in vitro activities of garenoxacin, a novel des-F (6)-quinolone, levofloxacin, moxifloxacin and clarithromycin were tested against 30 recent clinical isolates of Chlamydia pneumoniae. The minimal inhibitory concentration (MIC) at which 90% of the isolates were inhibited and the minimal bactericidal concentration (MBC) at which 90% of the isolates were killed by garenoxacin for C. pneumoniae was 0.03 mg/l (range 0.015–0.03 mg/l).     

Antimicrobial activities of macrolides against recent clinical isolates,and analysis of resistant mechanisms

We examined antibacterial activities of 4 kinds of macrolides, erythromycin (EM), clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM), against 6 bacterial species of clinical strains isoleted in 2002. Bacterial isolates used were each 50 strains of methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae and 43 strains of Streptococcus pneumoniae. S. agalactiae were derived from gynecological samples, and other species were isolated from respiratory specimens. Antimicrobial activities against S. aureus, S. pyogenes, S. agalactiae, M. catarrhalis and H. influenzae of 14-membered macrolides, such as EM and CAM, were higher than those of 16-membered macrolide, RKM. By contrast, against S. pneumoniae, RKM was more effective than 14-membered macrolides. Six, three and four strains of S. aureus, S. pyogenes and S. agalactiae, respectively, were resistant to macrolides. Thirty-five among 43 pneumococcal isolates were resistant, and 15 of the 35 were highly-resistant, MIC of > 128 micrograms/ml, to any one of EM, CAM or AZM. Isolation frequency of resistant strains to RKM was lower than those to 14- and 15-membered macrolides: only one strain was highly-resistant and 12 were intermediately-resistant. No resistant strain was recognized in M. catarrhalis and H. influenzae. Further, we analyzed the resistant mechanisms, methylation or efflux, of macrolide resistant strains by the double-disk method. Methylation was major mechanism in S. aureus, and in S. pyogenes, all of the resistance was caused by methylation. In S. agalactiae and S. pneumoniae, methylation and efflux shared about half and half.     

Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae

Chlamydia pneumoniae is responsible for respiratory tract infections of both upper and lower respiratory tract. Although this bacterium is one of the most wide-spread pathogens of man, there are limited data on the antibiotic treatment of C. pneumoniae infections. The aim of this study has been to evaluate the in vitro activity of thiamphenicol glycinate acetylcysteinate (TGA, CAS 20192-91-0) in comparison with molecules with established activity against C. pneumoniae, as well as macrolides and quinolones. The results have shown that TGA and clarithromycin (CAS 81103-11-9) are the most active drugs tested, but it is important to underline that the minimal inhibitory concentration (MIC) ranges of TGA are very much lower than the breakpoint of thlamphenicol for the respiratory pathogens. In conclusion, the good antimicrobial in vitro activity of TGA against C. pneumoniae together with its in vivo characteristics, in particular the high concentration reached in lung and the combination with the mucolytic agent N-acetylcysteine (NAC, CAS 616-91-1), can make a valid choice in the treatment of respiratory tract infections caused by C. pneumoniae. These findings need further evaluation by clinical studies.     

The resistance of recent clinical isolates against isepamycin, other aminoglycosides and injectable beta-lactams

Clinical isolates collected from clinical facilities across Japan in 1998 were tested against five aminoglycosides and three beta-lactams. The resistance of 50 strains each of methicillin sensitive Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter sp., Serratia sp., Pseudomonas aeruginosa and Proteus sp. (P. mirabilis 25 strains and P. vulgaris 25 strains) to the aminoglycosides isepamicin (ISP), amikacin (AMK), gentamicin, tobramycin and dibekacin, and to the beta-lactams imipenem, ceftazidime and piperacillin (all three known to be effective against P. aeruginosa) were investigated using a micro liquid dilution method with the following results: 1. ISP was effective against all strains except for 14% of MRSA, 2% of Proteus sp., and 4% of P. aeruginosa. 2. Six strains of MRSA were resistant to all eight drugs; however, in these cases ISP exhibited a relatively low minimum inhibitory concentration (MIC) compared to the other compounds. 3. Four strains of MRSA were resistant to all drugs except ISP. MRSA was the only isolate to demonstrate a resistance to seven or more drugs. 4. Twenty-one strains of MRSA and 1 strain of P. aeruginosa were resistant to six drugs; however, all of these were susceptible to both ISP and AMK. 5. Against all strains tested, ISP generally exhibited a lower MIC compared to AMK. These results suggest that, even ten years after its entering the market, ISP is still an aminoglycoside having a high anti-bacterial activity against a wide range of clinical isolates.     

In-vitro activity of cefoxitin against recent clinical bacterial isolates.

The susceptibility of 635 clinical isolates of bacteria to cefoxitin was determined. Isolates from the urinary tract showed 97% sensitivity, isolates from infected wounds showed 93% sensitivity and 82% of blood culture isolates were sensitive. Streptococcus faecalis isolates showed only 50% sensitivity and pseudomonas organisms were predominantly resistant. Bacteria isolated from unprepared heart valves submitted for use as homografts showed only 71% sensitivity due to the large proportion of Streptococcus and Pseudomonas species isolated.     

Antibacterial activity of biapenem against recent clinical isolates

Antibacterial activity of biapenem (BIPM) against clinical isolates of 8 species between 2000 and 2002 was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP) and ceftazidime (CAZ). The MICs of biapenem for Gram-positive bacteria were higher than those of IPM/CS and PAPM/BP, equal to those of MEPM and lower than those of CAZ. The MICs of BIPM for Gram-negative bacteria were higher than those of MEPM, equal to those of IPM/CS and PAPM/BP, and lower than those of CAZ. Antibacterial activity of BIPM against Pseudomonas aeruginosa was equal to those of IPM/CS and MEPM and superior to those of PAPM/BP and CAZ. In conclusion, BIPM showed broad antibacterial activity against both Gram-positive and Gram-negative clinical isolates. These results suggest that BIPM is useful for the treatment of various bacterial infections.     

Activity of ceftobiprole against Streptococcus pneumoniae isolates exhibiting high-level resistance to ceftriaxone

Tracking Resistance in the US Today (TRUST) 2008 surveillance data showed that 6% of Streptococcus pneumoniae were non-susceptible to ceftriaxone [minimum inhibitory concentration (MIC) ≥ 2 μg/mL] and that 8% of the ceftriaxone-non-susceptible isolates exhibited high-level resistance (MIC ≥ 8 μg/mL). Here we describe the activity of ceftobiprole against ceftriaxone-resistant isolates and characterise the genotypic traits associated with resistance. Thirty isolates with ceftriaxone MICs ≥ 8 μg/mL were analysed by sequencing of penicillin-binding protein (PBP) and murM genes. Sequencing of pbp1a, pbp2b and pbp2x showed nine PBP patterns, with the most common (n=17) being: PBP1a T371S (STMK motif), P432T (SRNVP motif); PBP2b T446A (SSNT motif), A619G (KTGTA motif); and PBP2x T338A and M339F (STMK motif), L364F, I371T, R384G, M400T, L546V (LKSGT motif); six isolates had the same pattern without the PBP2b A619G change. For these 23 isolates, MICs were 8 μg/mL for ceftriaxone, 4-8 μg/mL for penicillin and 0.5-2 μg/mL for ceftobiprole. The remaining seven isolates with higher MICs (ceftriaxone 8-32 μg/mL, penicillin 4-32 μg/mL and ceftobiprole 2-4 μg/mL) had fewer PBP active-site motif substitutions. The majority of isolates (17/30) had murM alleles similar to the wild-type, whilst the rest had alleles reflecting a mosaic structure. No murM alleles were associated with higher MICs. Against these 30 isolates, ceftobiprole was 4-16-fold more active than ceftriaxone. Widely described PBP and MurM substitutions probably account for the high ceftriaxone MICs (8 μg/mL) in the majority of isolates. However, seven isolates with ceftriaxone MICs of 8-32 μg/mL had fewer PBP substitutions in active-site motifs, suggesting either that there is another resistance mechanism or that unique PBP mutations may contribute to high-level β-lactam resistance.     

Streptococcus pneumoniae in Saudi Arabia: antibiotic resistance and serotypes of recent clinical isolates

During 2000, 154 clinical Streptococcus pneumoniae isolates were collected from or through three major hospitals serving the Western, Central, and Eastern regions of the Kingdom of Saudi Arabia. Ninety-one (59.1%) of the 154 isolates were resistant to penicillin with 23 strains (14.9%) highly resistant. Resistance was more prevalent among isolates obtained from patients <10 years of age and from isolates cultured from blood and cerebral spinal fluid. Decreased sensitivity to ceftriaxone, erythromycin, trimethoprim-sulphamethoxazole, and levofloxacin was found in 14.9, 15.6, 9.7, and 1.3% of isolates, respectively. There were no significant differences in the resistance pattern between isolates obtained from patients in the three different geographical areas. Serotypes of 116 isolates revealed the most prevalent types to be (descending order) 4, 3, 19F, 9V, 6A, 19A, 14 and 23F, comprising 75% of all strains typed; 9.5% of isolates were nontypable. S. pneumoniae isolates from Saudi Arabia have become more resistant to penicillin and other antimicrobials over the past 20 years.     

Susceptibility of recent clinical isolates to temafloxacin (A-63004) and other antimicrobial agents.

In vitro susceptibility of 1008 strains of recent clinical isolates was determined against the new aryl fluoroquinolone temafloxacin (T-167, A-63004) ciprofloxacin, norfloxacin, ampicillin, piperacillin, cephalothin, cefoxitin, ceftazidime, gentamicin, amikacin, oxacillin and vancomycin. The minimum inhibitory concentrations (MICs) of temafloxacin in micrograms/ml required for > or = 90% isolates were 0.13-0.5 for enterobacter, 0.03-0.25 for Escherichia coli, 0.12-0.5 for Klebsiella, 0.5-1.0 for Proteus mirabilis, 0.12-0.5 for Morganella morganii, 0.03-0.12 for Salmonella, 0.25-1.0 for Serratia marcescens, 0.03-0.12 for Shigella, 0.06-4.0 for Pseudomonas aeruginosa, 0.06-0.12 for Aeromonas hydrophila, 0.12-0.5 for Staphylococcus aureus, 0.12-1.0 for coagulase negative staphylococci and 4.0-8.0 for enterococci. The antibacterial activity of temafloxacin was comparable or superior to other drugs tested against most organisms. However, Xanthomonas malthophilia was relatively more susceptible to ciprofloxacin and norfloxacin, and temafloxacin had significantly high antibacterial activity against enterococci as compared to other fluoroquinolones.     

大环内酯类和氟喹诺酮类药物对细胞内嗜肺军团菌的效果分析

目的分析了大环内酯类和氟喹诺酮类药物在抑制巨噬细胞内嗜肺军团菌的疗效。方法选取10株不同嗜肺军团菌血清1型,利用琼脂稀释法对不同嗜肺军团菌血清1型针对大环内酯类和氟喹诺酮类药物的半致死浓度进行分析。THP-1人单核细胞在佛波酯诱导下形成巨噬细胞,然后将不同嗜肺军团菌血清1型与巨噬细胞共同培养,待细胞将巨噬细胞吞噬后,采用半致死浓度不同倍数(1倍、4倍,8倍)的红霉素、阿奇霉素、左氧氟沙星及莫西沙星等药物对胞内的细菌进行抑制,共同培养24 h后,采用平板计数法对军团数量进行计算,用细菌抑制率进行表示。结果红霉素、阿奇霉素、左氧氟沙星及莫西沙星在半致死剂量、4倍半致死剂量、8倍半致死剂量下对细菌的抑制情况如下:红霉素:(51.42±23.19)%、(75.28±19.08)%及(90.52±9.87)%;阿奇霉素:(60.57±23.14)%,(90.25±9.68)%及(98.58±3.89)%;左氧氟沙星:(99.24±0.13)%、(99.56±0.58)%及(99.99±0.01)%;莫西沙星:(99.14±0.25)%、(99.36±0.35)%及(99.89±0.11)%。在不同半致死剂量下氟喹诺酮类药物对巨噬细胞胞内细菌的抑制率明显高于大环内酯类药物,具有统计学意义(P<0.05)。左氧氟沙星和莫西沙星在不同倍数的半致死剂量下对细菌的抑制率没有显著性差异P>0.05),阿奇霉素对巨噬细胞内细菌的抑制率显著性高于于红霉素,具有显著统计学意义(P<0.05)。结论氟唾诺酮类药物抑制胞内抗军团菌效果好于大环内酯类药物,左氧氟沙星和莫西沙星抑制效果相当,阿奇霉素抑制效果明显优于红霉素。     

In vitro activity of GAR-936 against Chlamydia pneumoniae and Chlamydia trachomatis

We evaluated the in vitro activity of GAR-936, a novel glycylcycline antibiotic, against ten isolates of Chlamydia pneumoniae and five strains of C. trachomatis. Susceptibility testing was done in HEp-2 cells. The MIC90s and MBC90s of GAR-936, doxycycline, ofloxacin and clarithromycin against C. pneumoniae were 0.125, 0.25, 0.25 and 0.06 mg/l, respectively. The MICs and MBCs of GAR-936, doxycycline, ofloxacin and clarithromycin against C. trachomatis were 0.03-0.125, 0.25, 0.25-0.5 and 0.06 mg/l, respectively. GAR-936 had excellent activity against both chlamydial species and may have a potential role in the treatment of human chlamydial infection.     

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.     

Activity of telithromycin against erythromycin-susceptible and -resistant Streptococcus pneumoniae isolates from adults with invasive infections

A telithromycin (TEL) kill-kinetics study was conducted with 120 clinically significant Streptococcus pneumoniae isolates (60 susceptible and 60 highly resistant to erythromycin). Time–kill curves were performed using different antibiotic concentrations. The minimum inhibitory concentrations (MICs) of TEL were low for both erythromycin-susceptible (MIC ≤ 0.016 mg/L) and erythromycin-resistant strains (MIC ≤ 0.25 mg/L). TEL showed 99.9% killing of all erythromycin resistant strains at 18–24 h of incubation. Even for strains with erythromycin MICs ≥ 64.0 mg/L, TEL was uniformly bactericidal at 0.25 mg/L.     

头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性

目的　评价第四代头孢菌素头孢吡肟对 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性。方法　收集 2 0 0 1年 3～ 10月福州地区 4家医院分离的肺炎克雷伯氏菌和大肠埃希氏菌 4 2 6株 ,用 Kirby-Bauer琼脂扩散法作药敏试验 :用表型确认试验检测 ESBL s。结果　 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌中 ,头孢吡肟的敏感性为 94 .37% ,仅次于亚胺培南 (10 0 % )、头孢哌酮 /舒巴坦 (10 0 % )和哌拉西林 /三唑巴坦(99.5 3% ) ,明显高于青霉素类抗生素哌拉西林 (48.83% )和第二代头孢菌素头孢呋辛 (6 0 .0 9% ) ,也高于第三代头孢菌素头孢曲松 (6 2 .91% )、头孢噻肟 (6 4 .79% )、头孢哌酮 (6 5 .73% )和头孢他啶 (88.2 6 % )。经表型确认试验证实 14 2株 (33.33% )为产超广谱 β-内酰胺酶 (ESBL s)菌 ;头孢吡肟对产 ESBL s菌和非产 ESBL s菌体外敏感性分别为 84 .5 1%、99.30 %。结论　头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外抗菌活性高于第三代头孢菌素 ,低于亚胺培南、头孢哌酮 /舒巴坦和哌拉西林 /三唑巴坦 ,头孢吡肟可考虑作为医院内感染的经验性一线用药。     

192株肺炎链球菌对新喹诺酮体外耐药性测定

目的调查192株肺炎链球菌对青霉素、红霉素和环丙沙星等的耐药现状,并与新喹诺酮类进行比较.方法根据美国国家临床实验室标准委员会(NCCLS)标准使用微量肉汤稀释法检测192株肺炎链球菌对青霉素、红霉素、克林霉素和喹诺酮类抗菌药物的最低抑菌浓度(MIC).结果肺炎链球菌对青霉素的耐药率(中介率+耐药率)已达42.7%,对红霉素的耐药率为77.6%,克林霉素、白霉素、环丙沙星的耐药率分别为66.7%、65.6%、57.3%,新喹诺酮类抗菌药物对之有较好的抗菌活性,敏感率皆大于90%,与是否对青霉素、红霉素耐药无关.结论在我国,肺炎链球菌对青霉素、红霉素的耐药率较高,新喹诺酮类抗生素有较好的抗菌活性.     

In vitro study of the antibacterial activity of ofloxacin against recent clinical isolates

The in vitro activity of ofloxacin, a new broad-spectrum antimicrobial agent, was studied by a standardized single disc method. A total of 990 clinical isolates were tested, including 20 strains of anaerobic bacteria. Ofloxacin was highly active against 683 strains (70.41%), had intermediate activity against 109 (11.23%) and had no activity against 178 (18.35%). Ofloxacin was highly active against E. coli, Klebsiella sp., Citrobacter sp., Proteus mirabilis, Proteus morganii, Salmonella sp., Campylobacter jejuni, Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Eubacterium sp., Propionibacterium acnes and Streptococcus sp. Pseudomonas sp., Serratia sp. and Proteus vulgaris had percentages of resistance to ofloxacin of 37.11%, 32% and 33.33% respectively. High percentages of resistance to ofloxacin were found only for Providencia sp., Proteus rettgeri and Bacteroides fragilis. With regard to Streptococcus faecalis, the results obtained with the disc procedure were not reliable and MIC determination was necessary to assess the behaviour of the drug.